Aqueous metal bicarbonate solution and method of use

ABSTRACT

An aqueous neutral to mildly alkaline metal bicarbonate solution is disclosed. The solution comprises metal bicarbonate dissolved in the solution, the metal bicarbonate comprising bicarbonate anions and metal cations. In addition there is a pH adjusting agent in the solution in an amount whereby the solution is at a neutral to mildly alkaline pH. Also disclosed is a process of preparing an aqueous neutral to mildly alkaline metal bicarbonate solution comprising bicarbonate anions and metal cations. The process comprises reacting a compound selected from the group consisting of metal carbonate, metal carbonate hydroxide, metal oxide, metal hydroxide and any mixture thereof with an effective concentration of a pH adjusting agent to produce the aqueous neutral to mildly alkaline metal bicarbonate solution, wherein the pH adjusting agent is present in an amount whereby the solution is at a neutral to mildly alkaline pH. Further disclosed are a method of preventing and/or treating certain inflammatory diseases and/or degenerative diseases in a mammal, a method of preventing and/or treating certain viral diseases in a mammal, a method of decreasing and/or treating senescence and/or of increasing longevity in a mammal, a method of scavenging protons in a mammal, a method of decreasing proton concentrations in a mammal by altering carbonic anhydrase enzyme reactions in said mammal, a method of decreasing inflammation and/or inflammatory conditions in a mammal and a method of increasing motor activity and/or decreasing fatigue in a mammal.

TECHNICAL FIELD

[0001] This invention relates to an aqueous metal bicarbonate solution,a process of preparing the aqueous metal bicarbonate solution and amethod of preventing and treating certain inflammatory diseases,degenerative diseases and viral diseases in mammals. Generally thecertain inflammatory diseases, degenerative diseases and viral diseasesin mammals are those that require extracellular or intracellular acidicconditions or extracellular or intracellular proton concentrations atsome point in disease process or disease pathogenesis.

[0002] Typically the certain inflammatory diseases, degenerativediseases and viral diseases in mammals are those that require theactivities of carbonic anhydrase enzymes and/or the activities of acid(aspartic) protease enzymes and/or the activities of endosomal orlysosomal acid-requiring-enzymes and/or the activities of V-type ATPaseproton pumps at some point in disease process or disease pathogenesis.Typically the certain inflammatory diseases, degenerative diseases andviral diseases in mammals are represented by the diseases of arthritisand influenza.

[0003] This invention relates to a method of using an aqueous metalbicarbonate solution to decrease senescence and to increase longevity inmammals. Generally senescence is decreased and longevity is increased inmammals by improving the buffering capacity of the extracellular andintracellular fluids of the body. Generally senescence is decreased andlongevity is increased in mammals by the improved buffering capacitycausing a decrease in proton concentrations in the extracellular andintracellular fluids of the body. Typically senescence is decreased andlongevity is increased in mammals by improving the buffering capacity ofthe extracellular and intracellular bicarbonate buffers. Typicallysenescence is decreased and longevity is increased in mammals by theimproved extracellular and intracellular bicarbonate buffers causing adecrease in proton concentrations.

BACKGROUND ART

[0004] Certain inflammatory diseases, degenerative diseases and viraldiseases are major causes of morbidity and mortality in mammals.Typically these diseases are represented by the diseases of arthritisand influenza.

[0005] Arthritis is any inflammatory condition of the joints,characterised by pain and swelling. Osteoarthritis is the most commonform of arthritis in which one or many joints undergo degenerativechanges. Treatment includes rest of the involved joints, heat, andantiinflammatory drugs. Intraarticular injections of corticosteroids maygive relief. Surgical treatment is sometimes necessary and may reducepain and greatly improve the function of the joint. However thesetreatments, apart from surgical treatment, only provide temporary reliefand some may have severe side reactions

[0006] Influenza is a highly contagious infection of the respiratorytract caused by a myxovirus and transmitted by airborne dropletinfection. It occurs in isolated cases, epidemics and pandemics.Treatment is symptomatic and usually involves bed rest, antipyreticssuch as aspirin and drinking of fluids. New strains of the virus emergeat regular intervals so it is difficult to take preventative measures toavoid the infection. There is a need for a method to prevent and totreat certain inflammatory diseases, degenerative diseases and viraldiseases in mammals. There is a need for a method to prevent and totreat arthritis and influenza in mammals.

[0007] Senescence in mammals is characterised by progressive oxidationsof the structural and functional molecules that constitute body cellsand tissues. Oxidations of the structural and functional molecules inbody cells and tissues are increased in rate by acidic conditions.Oxidations of structural and functional molecules are increased in rateby the presence of excess proton concentrations. There is a need for amethod to prevent and treat excess proton concentrations in body cellsso that oxidations of structural and functional molecules are decreasedin rate. There is a need for a method to decrease and treat senescencein mammals.

OBJECTS OF INVENTION

[0008] It is an object of this invention to provide an aqueous metalbicarbonate solution to prevent and to treat certain inflammatorydiseases, degenerative diseases and viral diseases in mammals. It is afurther object of this invention to provide a process of preparing theaqueous metal bicarbonate solution. It is also an object of thisinvention to provide methods for the prevention and treatment of certaininflammatory diseases, degenerative diseases and viral diseases inmammals using the aqueous metal bicarbonate solution. Generally thecertain inflammatory diseases, degenerative diseases and viral diseasesin mammals are those that require extracellular or intracellular acidicconditions or extracellular or intracellular proton concentrations atsome point in disease process or disease pathogenesis. Typically thecertain inflammatory diseases, degenerative diseases and viral diseasesin mammals are those that require the activities of carbonic anhydraseenzymes and/or the activities of acid (aspartic) protease enzymes and/orthe activities of endosomal or lysosomal acid-requiring-enzymes and/orthe activities of V-type ATPase proton pumps at some point in diseaseprocess or disease pathogenesis. Typically the certain inflammatorydiseases, degenerative diseases and viral diseases in mammals arerepresented by the diseases of arthritis and influenza.

[0009] It is an object of tins invention to provide an aqueous metalbicarbonate solution to decrease senescence and to treat senescence andto increase longevity in manuals. It is a further object of thisinvention to provide a process of preparing the aqueous metalbicarbonate solution. It is also an object of this invention to providemethods for the decrease of senescence and the treatment of senescenceand the increase in longevity in mammals using the aqueous metalbicarbonate solution. Generally senescence is decreased and longevity isincreased in mammals by improving the buffering capacity of theextracellular and intracellular fluids of the body. Generally senescenceis decreased and longevity is increased in mammals by the improvedbuffering capacity causing a decrease in proton concentrations in theextracellular and intracellular fluids of the body. Typically senescenceis decreased and longevity is increased in mammals by improving thebuffering capacity of the extracellular and intracellular bicarbonatebuffers. Typically senescence is decreased and longevity is increased inmammals by the improved extracellular and intracellular bicarbonatebuffers causing a decrease in proton concentrations.

DISCLOSURE OF INVENTION

[0010] According to a first embodiment of the present invention there isprovided an aqueous metal bicarbonate solution comprising astoichiometric concentration of bicarbonate anions and a correspondingsubstantially stoichiometric concentration of metal cations inassociation with the bicarbonate anions, the metal bicarbonate beingpresent in a therapeutically effective amount and an acceptable carbondioxide-containing-aqueous diluent to maintain the metal bicarbonate inthe aqueous diluent.

[0011] Typically the solution is acceptable for oral administration.

[0012] In one embodiment there is provided a combination comprising thesolution of the first embodiment in combination with a stabilising agentin an amount effective to maintain and stabilise the bicarbonate anionsin the neutral to mildly alkaline solution. Generally the combination iskept in a sealed or closed container at 0.8 to 5 atmospheres, moretypically 1 atmosphere at 0-25° C., more typically 0.1-10° C. In oneparticular embodiment the stabilising agent may be present in thesolution in an amount effective to maintain and stabilise thebicarbonate anions in the neutral to mildly alkaline solution. Inanother particular embodiment the stabilising agent may consist of orcomprise a gas above the solution in an amount effective to maintain andstabilise the bicarbonate anions in the neutral to mildly alkalinesolution. In a further particular embodiment the stabilising agent maybe present in the solution and also may consist of or comprise a gasabove the solution, the total amount of stabilising agent in thesolution and in the gas above the solution being in an amount effectiveto maintain and stabilise the bicarbonate anions in the neutral tomildly alkaline solution. The stabilising agent which consists of a gasabove the solution may be carbon dioxide. The stabilising agent whichcomprises a gas above the solution may be carbon dioxide in an an inertgas such as nitrogen, air, oxygen, argon and/or helium, for example. Thestabilising agent in the solution may be carbon dioxide dissolved in thesolution, hydrated carbon dioxide, carbonic acid, and/or other suitablesource of carbon dioxide.

[0013] According to a second embodiment of the present invention thereis provided a process of preparing an aqueous metal bicarbonate solutioncomprising a stoichiometric concentration of bicarbonate anions and acorresponding substantially stoichiometric concentration of metalcations in association with the bicarbonate anions, which processcomprises reacting a concentration of a metal carbonate or metalcarbonate hydroxide or metal oxide or metal hydroxide with aconcentration of carbonic acid or hydrated carbon dioxide to produce themetal bicarbonate aqueous solution, wherein said metal bicarbonate beingpresent in a therapeutically effective amount.

[0014] Typically the aqueous metal bicarbonate solution has a neutral tomildly alkaline pH. Typically the pH is in the range 7 to 9. Typicallythe temperature of the aqueous metal bicarbonate solution is maintainedat a level to maintain the metal bicarbonate in the aqueous diluent.

[0015] According to a third embodiment of the present invention there isprovided an aqueous metal bicarbonate solution whenever prepared by theprocess of the second embodiment.

[0016] According to a fourth embodiment of the present invention thereis provided a method of preventing and treating certain inflammatorydiseases and degenerative diseases in a mammal in need of suchprevention or treatment comprising administering to said mammal aneffective at amount of an aqueous metal bicarbonate solution of thefirst or third embodiment or a metal bicarbonate.

[0017] Generally the certain inflammatory diseases and degenerativediseases in a mammal are those that require extracellular orintracellular acidic conditions or extracellular or intracellular protonconcentrations at some point in disease process or disease pathogenesis.

[0018] Typically the certain inflammatory diseases and degenerativediseases in a mammal are those that require the activities of carbonicanhydrase enzymes and/or the activities of acid (aspartic) proteaseenzymes and/or the activities of endosomal or lysosomalacid-requiring-enzymes and/or the activities of V-type ATPase protonpumps at some point in disease process or diseases pathogenesis.

[0019] Typically the certain inflammatory diseases or degenerativediseases may present as arthritis. Typically the arthritis may presentas osteoarthritis.

[0020] According to a fifth embodiment of the present invention there isprovided a method of preventing and treating certain viral diseases in amammal in need of such prevention or treatment comprising administeringto said mammal an effective amount of an aqueous metal bicarbonatesolution of the first or third embodiment or a metal bicarbonate.

[0021] Typically the certain viral diseases require intracellular acidicconditions or intracellular proton concentrations for either removal ofviral protein coats or assembly of viral protein coats. Typically theviral diseases may present as influenza.

[0022] According to a sixth embodiment of the present invention there isprovided a method of decreasing and treating senescence and ofincreasing longevity in a mammal comprising administering to said mammalan effective amount of an aqueous metal bicarbonate solution of thefirst or third embodiment or a metal bicarbonate.

[0023] Typically senescence is decreased and longevity is increased bymaintaining or increasing normal extracellular and/or intracellularalkaline conditions. Typically senescence is decreased and longevity isincreased by improving the buffering capacity of the extracellular andintracellular fluids of the body Typically longevity is increased bymaintaining or increasing normal mitochondrial alkaline conditions.Typically longevity is increased by decreasing extracellular andintracellular acidic conditions or by decreasing extracellular andintracellular proton concentrations.

[0024] Typically senescence is decreased and longevity is increased inmammals by improving the buffering capacity of the extracellular andintracellular bicarbonate buffers. Typically senescence is decreased andlongevity is increased in mammals by the improved extracellular andintracellular bicarbonate buffers causing a decrease in protonconcentrations. Typically senescence is decreased and longevity isincreased by preventing or treating certain inflammatory diseases,degenerative diseases and viral diseases in mammals. Typically longevityis increased by decreasing the morbidity and mortality associated withthese diseases.

[0025] According to a seventh embodiment of the present invention thereis provided a method of scavenging protons in a mammal comprisingadministering to said mammal an effective amount of a proton scavenger.

[0026] Typically the proton scavenger comprises a metal bicarbonate.Typically the metal bicarbonate is in the form of the aqueous metalbicarbonate solution of the first or third embodiment.

[0027] According to an eighth embodiment of the present invention thereis provided a method of decreasing proton concentrations in a mammal byaltering carbonic anhydrase enzyme reactions in said mammal comprisingadministering to said mammal an effective amount of an aqueous metalbicarbonate solution of the first or third embodiment or a metalbicarbonate.

[0028] According to a ninth embodiment of the present invention there isprovided a method of decreasing inflammation and inflammatory conditionsin a mammal comprising administering to said mammal an effective amountof an aqueous metal bicarbonate solution of the first or thirdembodiment or a metal bicarbonate.

[0029] Generally inflammation and inflammatory conditions are decreasedby decreasing the extracellular and intracellular acidic conditions thatare required for inflammatory processes. Generally inflammation andinflammatory conditions are decreased by decreasing the extracellularand intracellular proton concentrations that are required forinflammatory processes. Typically inflammation is decreased by alteringcarbonic anhydrase enzyme reactions and/or decreasing the activities ofacid (aspartic) protease enzymes and/or decreasing the activities ofendosomal or lysosomal acid-requiring-enzymes and/or decreasing theactivities of V-type ATPase proton pumps.

[0030] According to a tenth embodiment of the present invention there isprovided a method of increasing motor activity in a mammal comprisingadministering to said mammal an effective amount of an aqueous metalbicarbonate solution of the first or third embodiment or a metalbicarbonate.

[0031] Typically motor activity is increased by decreasing extracellularand intracellular acidic conditions or by decreasing extracellular andintracellular proton concentrations. Typically motor activity isincreased by improving the buffering capacity of extracellular andintracellular fluids. Typically motor activity is increased by improvingthe buffering capacity of the extracellular and intracellularbicarbonate buffers. Typically motor activity is increased by increasingextracellular and intracellular alkaline conditions.

[0032] Typically motor activity is increased by scavenging protonsproduced by ATP hydrolysis, lactic acid production, lipid metabolism andother metabolic processes.

[0033] According to an eleventh embodiment of the present inventionthere is provided an aqueous neutral to mildly alkaline metalbicarbonate solution, comprising metal bicarbonate dissolved in thesolution, said metal bicarbonate comprising bicarbonate anions and metalcations, and a pH adjusting agent in the solution in an amount wherebythe solution is at a neutral to mildly alkaline pH.

[0034] Typically a corresponding substantially stoichiometricconcentration of metal cations are in association with the bicarbonateanions. Typically the solution is acceptable for oral administration.

[0035] In one embodiment there is provided a combination comprising asubstantially stable aqueous neutral to mildly alkaline metalbicarbonate solution, comprising metal bicarbonate dissolved in thesolution, said metal bicarbonate comprising bicarbonate anions and metalcations, and a pH adjusting agent in the solution in an amount wherebythe solution is at a neutral to mildly alkaline pH, in combination witha stabilising agent in an amount effective to maintain and stabilise thebicarbonate anions in the neutral to mildly alkaline solution. Inanother embodiment there is provided a combination comprising asubstantially stable aqueous neutral to mildly alkaline metalbicarbonate solution, comprising metal bicarbonate dissolved in thesolution, said metal bicarbonate comprising bicarbonate anions and metalcations, in combination with a stabilising agent in an amount effectiveto maintain and stabilise the bicarbonate anions in the solution wherebythe solution is at a neutral to mildly alkaline pH.

[0036] The pH adjusting agent and the stabilising agent may be the sameor different. Generally the combination is kept in a sealed or closedcontainer at 0.8 to 5 atmospheres, more typically 1 atmosphere at 0-25°C., more typically 0.1-10° C.

[0037] In one particular embodiment the stabilising agent may be presentin the solution in an amount effective to maintain and stabilise thebicarbonate anions in the neutral to mildly alkaline solution. Inanother particular embodiment the stabilising agent may consist of orcomprise a gas above the solution in an amount effective to maintain andstabilise the bicarbonate anions in the neutral to mildly alkalinesolution. In a further particular embodiment the stabilising agent maybe present in the solution and may consist of or comprise a gas abovethe solution, the total amount of stabilising agent in the solution andin the gas above the solution being in an amount effective to maintainand stabilise the bicarbonate anions in the neutral to mildly alkalinesolution. The stabilising agent which consists of a gas above thesolution may be carbon dioxide. The stabilising agent which comprises agas above the solution may be carbon dioxide in an an inert gas such asnitrogen, air, oxygen, argon and/or helium, for example. The stabilisingagent in the solution may be carbon dioxide dissolved in the solution,hydrated carbon dioxide, carbonic acid, and/or other suitable source ofcarbon dioxide.

[0038] According to a twelfth embodiment of the present invention thereis provided a solution for preventing and/or treating certaininflammatory diseases and/or degenerative diseases and/or certain viraldiseases in a mammal, comprising the aqueous neutral to mildly alkalinemetal bicarbonate solution of the eleventh embodiment whereby the metalbicarbonate is present in an amount effective to prevent and/or treatsaid diseases.

[0039] According to a thirteenth embodiment of the present inventionthere is provided a solution for decreasing and/or treating senescenceand/or increasing longevity in a mammal, comprising the aqueous neutralto mildly alkaline metal bicarbonate solution of the eleventh embodimentwhereby the metal bicarbonate is present in an amount effective todecrease and/or treat senescence and/or increase longevity.

[0040] According to a fourteenth embodiment of the present inventionthere is provided a solution for scavenging protons in a mammal,comprising the aqueous neutral to mildly alkaline metal bicarbonatesolution of the eleventh embodiment whereby the metal bicarbonate ispresent in an amount effective to scavenge protons.

[0041] According to a fifteenth embodiment of the present inventionthere is provided a solution for decreasing proton concentrations in amammal, comprising the aqueous neutral to mildly alkaline metalbicarbonate solution of the eleventh embodiment whereby the metalbicarbonate is present in an amount effective to decrease protonconcentrations.

[0042] According to a sixteenth embodiment of the present inventionthere is provided a solution for decreasing inflammation andinflammatory conditions in a mammal, comprising the aqueous neutral tomildly alkaline metal bicarbonate solution of the eleventh embodimentwhereby the metal bicarbonate is present in an amount effective todecrease inflammation and/or inflammatory conditions.

[0043] According to a seventeenth embodiment of the present inventionthere is provided a solution for increasing motor activity and/ordecrease fatigue in a mammal, comprising the aqueous neutral to mildlyalkaline metal bicarbonate solution of the eleventh embodiment wherebythe metal bicarbonate is present in an amount effective to increasemotor activity.

[0044] According to an eighteenth embodiment of the present inventionthere is provided a process of preparing an aqueous neutral to mildlyalkaline metal bicarbonate solution comprising bicarbonate anions andmetal cations, which process comprises reacting a compound selected fromthe group consisting of metal carbonate, metal carbonate hydroxide,metal oxide, metal hydroxide and any mixture thereof with an effectiveconcentration of a pH adjusting agent to produce the aqueous neutral tomildly alkaline metal bicarbonate solution, wherein the pH adjustingagent is present in an amount whereby the solution is at a neutral tomildly alkaline pH.

[0045] Typically a corresponding substantially stoichiometricconcentration of metal cations are in association with the bicarbonateanions. Generally the solution is stored in a sealed or closed containerat 0.8 to 5 atmospheres, more typically 1 atmosphere at 0-25° C., moretypically 0.1-10° C. In one embodiment the process further comprisescombining the solution with a stabilising agent in an amount effectiveto maintain and stabilise the bicarbonate anions in the neutral tomildly alkaline solution. In one particular embodiment the processcomprises conducting the process under gaseous atmosphere comprising astabilising agent in an amount effective to maintain and stabilise thebicarbonate anions in the neutral to mildly alkaline solution. Thestabilising agent may be carbon dioxide or comprise carbon dioxide in aninert gas such as nitrogen, air, oxygen, argon and/or helium, forexample. Generally the combination is stored in a sealed or closedcontainer at 0.8 to 5 atmospheres, more typically 1 atmosphere at 0-25°C., more typically 0.1-10° C.

[0046] One particular embodiment may comprise adding the stabilisingagent to the solution in the solution in an amount effective to maintainand stabilise the bicarbonate anions in the neutral to mildly alkalinesolution. Another particular embodiment may comprise blanketing thesolution with a gas consisting of or comprising the stabilising agent inan amount effective to maintain and stabilise the bicarbonate anions inthe neutral to mildly alkaline solution. A further particular embodimentmay comprise adding the stabilising agent to the solution in thesolution and blanketing the solution with a gas consisting of orcomprising the stabilising agent, the total amount of stabilising agentin the solution and in the gas above the solution being in an amounteffective to maintain and stabilise the bicarbonate anions in theneutral to mildly alkaline solution. The stabilising agent whichconsists of a gas above the solution may be carbon dioxide. Thestabilising agent which comprises a gas above the solution may be carbondioxide in an inert gas such as nitrogen, air, oxygen, argon and/orhelium, for example. The stabilising agent in the solution may be carbondioxide dissolved in the solution, hydrated carbon dioxide, carbonicacid, and/or other suitable source of carbon dioxide.

[0047] According to a nineteenth embodiment of the present inventionthere is provided a aqueous neutral to mildly alkaline metal bicarbonatesolution whenever prepared by the process of the eighteenth embodiment.

[0048] According to a twentieth embodiment of the present inventionthere is provided a method of preventing and/or treating certaininflammatory diseases and/or degenerative diseases in a mammal in needof such prevention and/or treatment comprising administering to saidmammal an effective amount of an aqueous neutral to mildly alkalinemetal bicarbonate solution of the eleventh or a metal bicarbonate.

[0049] Generally the certain inflammatory diseases and degenerativediseases in a mammal are those that require extracellular orintracellular acidic conditions or extracellular or intracellular protonconcentrations at some point in disease process or disease pathogenesis.

[0050] Typically the certain inflammatory diseases and degenerativediseases in a mammal are those that require the activities of carbonicanhydrase enzymes and/or the activities of acid (aspartic) proteaseenzymes and/or the activities of endosomal or lysosomalacid-requiring-enzymes and/or the activities of V-type ATPase protonpumps at some point in disease process or disease pathogenesis.

[0051] Typically the certain inflammatory diseases or degenerativediseases may present as arthritis. Typically the arthritis may presentas osteoarthritis.

[0052] According to a twenty-first embodiment of the present inventionthere is provided a method of preventing and/or treating certain viraldiseases in a mammal in need of such prevention and/or treatmentcomprising administering to said mammal an effective amount of anaqueous neutral to mildly alkaline metal bicarbonate solution of theeleventh embodiment or a metal bicarbonate.

[0053] Typically the certain viral diseases require intracellular acidicconditions or intracellular proton concentrations for either removal ofviral protein coats or assembly of viral protein coats. Typically theviral diseases may present as influenza.

[0054] According to a twenty-second embodiment of the present inventionthere is provided a method of decreasing and/or treating senescenceand/or of increasing longevity in a mammal comprising administering tosaid mammal an effective amount of an aqueous neutral to mildly alkalinemetal bicarbonate solution of the eleventh embodiment or a metalbicarbonate.

[0055] Typically senescence is decreased and longevity is increased bymaintaining or increasing normal extracellular and/or intracellularalkaline conditions. Typically senescence is decreased and longevity isincreased by improving the buffering capacity of the extracellular andintracellular fluids of the body. Typically longevity is increased bymaintaining or increasing normal mitochondrial alkaline conditions.Typically longevity is increased by decreasing extracellular andintracellular acidic conditions or by decreasing extracellular andintracellular proton concentrations. Typically senescence is decreasedand longevity is increased in mammals by improving the bufferingcapacity of the extracellular and intracellular bicarbonate buffers.Typically senescence is decreased and longevity is increased in mammalsby the improved extracellular and intracellular bicarbonate bufferscausing a decrease in proton concentrations.

[0056] Typically senescence is decreased and longevity is increased bypreventing or treating certain inflammatory diseases, degenerativediseases and viral diseases in mammals.

[0057] Typically longevity is increased by decreasing the morbidity andmortality associated with these diseases.

[0058] According to a twenty-third embodiment of the present inventionthere is provided a method of scavenging protons in a mammal comprisingadministering to said mammal an effective amount of a proton scavenger.

[0059] Typically the proton scavenger comprises a metal bicarbonate.Typically the metal bicarbonate is in the form of the aqueous neutral tomildly alkaline metal bicarbonate solution of the eleventh embodiment.

[0060] According to a twenty-fourth embodiment of the present inventionthere is provided a method of decreasing proton concentrations in amammal by altering carbonic anhydrase enzyme reactions in said mammalcomprising administering to said mammal an effective amount of anaqueous neutral to mildly alkaline metal bicarbonate solution of theeleventh embodiment or a metal bicarbonate.

[0061] According to a twenty-fifth embodiment of the present inventionthere is provided a method of decreasing inflammation and/orinflammatory conditions in a mammal comprising administering to saidmammal an effective amount of an aqueous neutral to mildly alkalinemetal bicarbonate solution of the eleventh embodiment or a metalbicarbonate.

[0062] Generally inflammation and inflammatory conditions are decreasedby decreasing the extracellular and intracellular acidic conditions thatare required for inflammatory processes. Generally inflammation andinflammatory conditions are decreased by decreasing the extracellularand intracellular proton concentrations that are required forinflammatory processes. Typically inflammation is decreased by alteringcarbonic anhydrase enzyme reactions and/or decreasing the activities ofacid (aspartic) protease enzymes and/or decreasing the activities ofendosomal or lysosomal acid-requiring-enzymes and/or decreasing theactivities of V-type ATPase proton pumps.

[0063] According to a twenty-sixth embodiment of the present inventionthere is provided a method of increasing motor activity and/ordecreasing fatigue in a mammal comprising administering to said mammalan effective amount of an aqueous neutral to mildly alkaline metalbicarbonate solution of the eleventh embodiment or a metal bicarbonate.

[0064] The methods of the invention typically involve orallyadministering to the mammal, the mammal being typically human. Furtherthe methods of the invention typically involve orally administering to amammal in need of treatment for the specified condition of theparticular embodiment, the mammal being typically human. Typically motoractivity is increased by decreasing extracellular and intracellularacidic conditions or by decreasing extracellular and intracellularproton concentrations. Typically motor activity is increased byimproving the buffering capacity of extracellular and intracellularfluids. Typically motor activity is increased by improving the bufferingcapacity of the extracellular and intracellular bicarbonate buffers.Typically motor activity is increased by increasing extracellular andintracellular alkaline conditions. Typically motor activity is increasedby scavenging protons produced by ATP hydrolysis, lactic acidproduction, lipid metabolism and other metabolic processes.

[0065] The term mammal as used herein includes vertebrate. Examples ofmammals and vertebrates to which the methods of the invention applyinclude a bovine, human (male or female), ovine, equine, caprine,Leporine, feline or canine mammal or vertebrate. Specific examples ofanimals include sheep, cattle, horses, rabbits, cats, goats, alpacas,cats, dogs, pigs, rabbits, fowls, deer, buffaloes and other livestockand domestic animals.

[0066] Metal Bicarbonate Generally

[0067] Generally the pH of the aqueous metal bicarbonate solution isneutral to mildly alkaline, typically mildly alkaline and more typicallyin the range of 7 to 9 even more typically 8 to 8.6 and the temperatureof the aqueous neutral to mildly alkaline metal bicarbonate solution ismaintained at such a level so as to maintain the metal bicarbonate inthe aqueous diluent. The aqueous neutral to mildly alkaline metalbicarbonate solution may be kept under an atmosphere comprising carbondioxide of from about 0.8 to 5 or 1 to 5 atmospheres, more typically 1to 3 atmospheres and even more typically slightly above atmosphericpressure such as the sorts of pressures that soft drinks are currentlyunder in cans or bottles, for example, so as to maintain the metalbicarbonate in the aqueous diluent.

[0068] Generally the metal cation is an alkaline earth metal cation oran alkali metal cation.

[0069] Generally a metal cation is chosen which is capable of acting asa bicarbonate transporter into mammalian cells. More particularly themetal cation may be cations of magnesium, sodium, potassium, calcium,lithium or any mixture thereof. Where a mixture of alkaline earth metalcations or alkali metal cations are used: (1) two different alkalineearth metal cations or alkali metal cations or mixtures thereof, themolar ratio of the first metal cation to the second may be in the range0.5:99.5 to 99.5:0.5, typically 75:25 to 25:75, more typically 0.7:1 to1:0.7; (2) three different alkaline earth metal cations or alkali metalcations or mixtures thereof, the molar ratio of the first metal cationto the second to the third may be in the range 99.5:0.5:0.5 to0.5:99.5:99.5, typically 75:25:25 to 25:75:75, more typically 0.5:1:1 to1:0.5:0.5; (3) four different alkaline earth metal cations or alkalimetal cations or mixtures thereof, the molar ratio of the first metalcation to the second to the third to the fourth may be in the range99.5:0.5:0.5:0.5 to 0.5:99.5:99.5:99.5, typically 75:25:25:25 to25:75:75:75, more typically 0.5:1:1:1 to 0.5:1:1:1. Generally the metalcation is magnesium or a mixture of magnesium and sodium metal cations.Typically the aqueous neutral to mildly alkaline metal bicarbonatesolution has a high metal cation concentration in association withbicarbonate anions.

[0070] Typically the metal bicarbonate is used at a concentration of10-100 mole % or weight % of its saturation solubility (which willdepend on the actual metal bicarbonate(s) used), more typically 10-90%,10-80%, 10-70%, 10-60%, 10-50%, 10-40%, 10-30%, 10-20%, more typically15-95%, 15-85%, 15-75%, 15-65%, 15-55%, 15-45%, 15-35%, 15-25%, moretypically 15-90%, 15-80%, 15-70%, 15-60%, 15-50%, 15-40%, 15-30%,15-20%, more typically 10-95%, 10-85%, 10-75%, 10-65%, 10-55%, 10-45%,10-35%, 10-25%, more typically 20-90%, 20-80%, 20-70%, 20-60%, 20-50%,20-40%, 20-30%, more typically 25-95%, 25-85%, 25-75%, 25-65%, 25-55%,25-45%, 25-35%, more typically 25-90%, 25-80%, 25-70%, 25-60%, 25-50%,25-40%, 25-30%, more typically 20-95%, 20-85%, 20-75%, 20-65%, 20-55%,20-45%, 20-35%, more typically 30-90%, 30-80%, 30-70%, 30-60%, 30-50%,30-40%, more typically 35-95%, 35-85%, 35-75%, 35-65%, 35-55%, 35-45%,more typically 35-90%, 35-80%, 35-70%, 35-60%, 35-50%, 35-40%, moretypically 30-95%, 30-85%, 30-75%, 30-65%, 30-55%, 30-45%, more typically40-90%, 40-80%, 40-70%, 40-60%, 40-50%, more typically 45-95%, 45-85%,45-75%, 45-65%, 45-55%, more typically 45-90%, 45-80%, 45-70%, 45-60%,45-50%, more typically 40-95%, 40-85%, 40-75%, 40-65%, 40-55%, moretypically 50-90%, 50-80%, 50-70%, 50-60%, more typically 55-95%, 55-85%,55-75%, 55-65%, more typically 55-90%, 55-80%, 55-70%, 55-60%, moretypically 50-95%, 50-85%, 50-75%, 50-65%, more typically 60-90%, 60-80%,60-70%, more typically 65-95%, 65-85%, 65-75%, more typically 65-90%,65-80%, 65-70%, more typically 60-95%, 60-85%, 60-75%, more typically70-90%, 70-80%, more typically 75-95%, 75-85%, more typically 75-90%,75-80%, more typically 70-95%, 70-85%, more typically 80-90%, moretypically 85-95%, more typically 85-90%, more typically 80-95%, moretypically 20-100%, 30-100%, 40-100%, 50-100%, 60-100%, 70-100%, 80-100%or 90-100%. Depending on the solubility of the metal bicarbonate, theamount of metal cation may range from 20 mg to 1250 mg or 25 mg to 1250mg per litre of aqueous neutral to mildly alkaline metal bicarbonatesolution, typically 20 mg to 1000 mg or 50 mg to 1000 mg per litre ofaqueous neutral to mildly alkaline metal bicarbonate solution, moretypically 20 mg to 750 mg or 50 mg to 750 mg or 20 mg to 600 mg or 50 mgto 600 mg per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, even more typically 20 mg to 500 mg or 30 mg to500 mg or 50 mg to 500 mg per litre of aqueous neutral to mildlyalkaline metal bicarbonate solution, even more typically 20 mg to 250 mgor 50 mg to 250 mg per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, most typically 100 mg to 500 mg or 100 mg to 400mg or 100 mg to 300 mg or 100 mg to 250 mg per litre of aqueous neutralto mildly alkaline metal bicarbonate solution, even most typically 20 mgto 200 mg or 20 to 150 mg or 20 mg to 120 mg or 120 mg to 300 mg or 120mg to 200 mg. Typically when the metal cation is magnesium, the amountof magnesium may range from 30 mg to 140 mg per litre of aqueous neutralto mildly alkaline metal bicarbonate solution, typically 30 mg to 130mg, 30 mg to 120 mg, 30 mg to 110 mg, 30 mg to 100 mg, 30 mg to 90 mg,30 mg to 80 mg, 30 mg to 70 mg, 30 mg to 60 mg, 30 mg to 50 mg, 30 mg to40 mg, 50 mg to 120 mg, 60 mg to 120 mg, 70 mg to 120 mg, 80 mg to 120mg, 90 mg to 120 mg or 75 mg to 120 mg or 100 mg to 120 mg per litre ofaqueous neutral to mildly alkaline metal bicarbonate solution. Typicallywhen the metal cation is sodium and/or potassium, the amount of sodiumand/or potassium may range from greater than 30 mg to 1250 mg per litreof aqueous neutral to mildly alkaline metal bicarbonate solution,typically 50 mg to 1000 mg or 50 mg to 750 mg or 50 mg to 500 mg or 75mg to 1250 mg or 75 mg to 1000 mg or 75 mg to 500 mg or 100 mg to 1000mg or 100 mg to 500 mg or 250 mg to 1000 mg or 250 mg to 500 mg perlitre of aqueous neutral to mildly alkaline metal bicarbonate solution.Typically when the metal cation is calcium, the amount of calcium mayrange from greater than 20 mg to 1250 mg per litre of aqueous neutral tomildly alkaline metal bicarbonate solution, typically 20 mg to 1000 mgor 20 mg to 750 mg or 20 mg to 500 mg or 20 mg to 250 mg or 20 mg to 200mg or 20 mg to 150 mg or 20 mg to 100 mg per litre of aqueous neutral tomildly alkaline metal bicarbonate solution. Typically the amount ofbicarbonate anion present will be stoichiometric with the amount ofmetal cation in solution so as to form the metal bicarbonate.Alternatively, the concentration of the metal bicarbonate can be basedon the bicarbonate anion concentrations in which case the amount ofbicarbonate anion (which will depend on the saturation solubility of theactual metal bicarbonate anion(s) used). The concentration ofbicarbonate typically ranges from 120 mg or 150 mg to 3500 mg per litreof aqueous neutral to mildly alkaline metal bicarbonate solution,typically 120 mg or 150 mg to 3000 mg or 200 mg to 3000 mg per litre ofaqueous neutral to mildly alkaline metal bicarbonate solution, moretypically 250 mg to 2100 mg or 300 mg to 2000 mg or 200 mg to 1500 mg or300 mg to 1500 mg or 400 mg to 1500 mg or 500 mg to 1500 mg or 600 mg to1500 mg or 700 mg to 1500 mg or 800 mg to 1500 mg or 900 mg to 1500 mgor 1000 mg to 1500 mg or 200 mg to 1000 mg or 300 mg to 1000 mg or 400mg to 1000 mg or 500 mg to 1000 mg or 600 mg to 1000 mg or 700 mg to1000 mg or 800 mg to 1000 mg or 900 mg to 1000 mg or 1000 mg to 1500 mgor 1200 mg to 1500 mg per litre of aqueous neutral to mildly alkalinemetal bicarbonate solution, even more typically 600 mg to 1000 mg or 500mg to 1500 mg per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, most typically 950 mg or 200 mg to 2000 mg or 200mg to 1750 mg or 200 mg to 1250 mg or 200 mg to 100 mg per litre ofaqueous neutral to mildly alkaline metal bicarbonate solution. Typicallyat least 600 mg of bicarbonate anions per litre of solution is present,more typically 600-1800 mg/l, 600-1500 mg/l, 600-1350 mg/l, 600-1200mg,/l 600-1100 mg/l, 600-1000 mg/l, 600-950 mg/l, 600-900 mg/l, 600-850mg/l, 600-800 mg/l, 600-750 mg/l, 600-700 mg/l or 600-650 mg/l.Typically a mildly alkaline saturated magnesium bicarbonate solution isused or a mildly alkaline solution comprising a mixture of sodium and/orpotassium and magnesium bicarbonate, more typically sodium and magnesiumbicarbonate. Typically the range for a mixture of sodium and/orpotassium and magnesium bicarbonate, more typically sodium and magnesiumbicarbonate varies from 20 mg to 1250 mg or 25 mg to 1250 mg per litreof aqueous neutral to mildly alkaline metal bicarbonate solution,typically 20 mg to 1000 mg or 50 mg to 1000 mg per litre of aqueousneutral to mildly alkaline metal bicarbonate solution, more typically 20mg to 750 mg or 50 mg to 750 mg or 20 mg to 600 mg or 50 mg to 600 mgper litre of aqueous neutral to mildly alkaline metal bicarbonatesolution, even more typically 20 mg to 500 mg or 30 mg to 500 mg or 50mg to 500 mg per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, even more typically 20 mg to 250 mg or 50 mg to250 mg or even more typically 20 mg to 300 mg or 50 mg to 300 mg perlitre of aqueous neutral to mildly alkaline metal bicarbonate solution,most typically 75 mg to 1000 mg or 75 mg to 500 mg or 100 mg to 1000 mgor 100 mg to 500 mg or 100 mg to 400 mg or 100 mg to 300 mg or 100 mg to250 mg per litre of aqueous neutral to mildly alkaline metal bicarbonatesolution, even most typically 20 mg to 200 mg or 20 to 150 mg or 200 mgto 120 mg or 120 mg to 300 mg or 120 mg to 200 mg. Usually the ratio(weight to weight) of magnesium to sodium is in the range 25:1 to 1:4,typically 1:1.125.

[0071] Generally the aqueous diluent is water or comprises water.Generally the carbon dioxide-containing-aqueous diluent may be carbonicacid in water, hydrated carbon dioxide in water, carbon dioxide gasdissolved in water, carbonated soft drinks, carbonated mineral water,soda water or other carbon dioxide-containing-aqueous diluents. Ifcarbon dioxide gas is used, the carbon dioxide may be either bubbledinto aqueous solutions containing metal carbonate or metal carbonatehydroxide or metal oxide or mixture thereof or the carbon dioxide may beintroduced in the form of a blanket over aqueous solutions containingmetal carbonate or metal carbonate hydroxide or metal oxide or mixturethereof. Typically the carbon dioxide-containing-aqueous diluent ispharmaceutically acceptable. Typically carbonated mineral water,carbonic acid, hydrated carbon dioxide in water or carbonated water isused. The amounts of carbon dioxide-containing-aqueous diluent and metalcarbonate or metal carbonate hydroxide or metal oxide or mixture thereofused are sufficient to obtain a clear solution at a neutral to mildlyalkaline pH, typically pH 7 to 9 or pH 7 to 8.6, more typically pH 7.5to 8.8 or pH 7.5 to 8.5 or pH 7.8 to 8.6, pH 7.8 to 8.5, pH 7.8 to 8.4,pH 7.8 to 8.3, pH 7.8 to 8.2, pH 7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to7.9, pH 7.9 to 8.6, pH 7.9 to 8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH 7.9to 8.2, pH 7.9 to 8.1, pH 7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH8.0 to 8.4, pH 8.0 to 8.3, pH 8.0 to 8.2, pH 8.0 to 8.1, pH 8.1 to 8.6,pH 8.1 to 8.5, pH 8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH 8.2 to8.6, pH 8.2 to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to 8.6, pH 8.3to 8.5, pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH 8.5 to 8.6, evenmore typically pH 8 to 8.5 or pH 8.2 to 8.6, most typically pH 8.3.Usually 10 to 60 mL, typically 25 to 55 mL, more typically 40 to 50 mL,most typically approximately 45 mL of chilled carbonated mineral waterper litre of water is used. Usually the chilled carbonated mineral wateris at a temperature of 0 to 25° C., 0 to 20° C., 0.5 to 25° C., 0.5 to20° C., 0.5 to 15° C., 0.5 to 10° C., 0.5 to 9° C., 0.5 to 8° C., 0.5 to7° C., 1 to 20° C., 1 to 15° C., 1 to 10° C., 1.5 to 20° C., 1.5 to 15°C., 1.5 to 10° C., 2 to 20° C., 2 to 15° C., 2 to 10° C., 3 to 20° C., 3to 15° C., 4 to 20° C., 4 to 15° C., 4 to 10° C., 5 to 20° C., 5 to 15°C., 6 to 20° C., 6 to 15° C., 6 to 10° C., 7 to 20° C., 7 to 15° C., 7to 10° C., 8 to 20° C., 8 to 15° C., 8 to 10° C., 9 to 20° C., 9 to 15°C., 9 to 10° C., 10 to 15° C., typically 0 to 15° C., more typically 0to 10° C., even more typically 3° C. to 10° C., most typically 5° C. to10° C. and even most typically 5° C. Alternatively the metal carbonateor metal carbonate hydroxide or metal oxide or mixture thereof can beadded after the carbon dioxide has been added.

[0072] Generally the metal bicarbonate in aqueous solution may bederived from a metal carbonate or metal carbonate hydroxide or metaloxide or metal bicarbonate or metal, hydroxide or other appropriatemetal compound or any mixture thereof. Examples include magnesium,sodium, potassium, calcium, lithium carbonate or carbonate hydroxide oroxide or bicarbonate or a mixture of any two or more thereof. Forexample magnesium carbonate hydroxide pentahydrate, the calcite seriesor dolomite series of minerals (Mg, Ca)CO₃ or limestone or dolomiterocks is used. Generally magnesium carbonate hydroxide pentahydrate or amixture of magnesium carbonate hydroxide pentahydrate and sodiumbicarbonate is used.

[0073] Generally the pH of the aqueous metal bicarbonate solution fororal administration is neutral to mildly alkaline, typically in therange pH 7 to 9 or pH 7 to 8.6, more typically pH 7.5 to 8.8 or pH 7.5to 8.5 or pH 7.8 to 8.6, pH 7.8 to 8.5, pH 7.8 to 8.4, pH 7.8 to 8.3, pH7.8 to 8.2, pH 7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to 7.9, pH 7.9 to 8.6,pH 7.9 to 8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH 7.9 to 8.2, pH 7.9 to8.1, pH 7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH 8.0 to 8.4, pH 8.0to 8.3, pH 8.0 to 8.2, pH 8.0 to 8.1, pH 8.1 to 8.6, pH 8.1 to 8.5, pH8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH 8.2 to 8.6, pH 8.2 to 8.5,pH 8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to 8.6, pH 8.3 to 8.5, pH 8.3 to8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH 8.5 to 8.6, even more typically pH8 to 8.5 or pH 8.2 to 8.6, most typically pH 8.3. Generally the pH ofthe aqueous metal bicarbonate solution for parenteral administration isneutral to very mildly alkaline, typically in the range pH 7 to 7.6, orpH 7.0 to 7.5, or pH 7.1 to 7.5, more typically pH 7.2 to 7.5 or pH 7.3to 7.5 or pH 7.4 to 7.5. Generally the aqueous neutral to mildlyalkaline metal bicarbonate solution is prepared and stored at atemperature ranging from 0 to 25° C., 0 to 20° C., 0.5 to 25° C., 0.5 to20° C., 0.5 to 15° C., 0.5 to 10° C., 0.5 to 9° C., 0.5 to 8° C., 0.5 to7° C., 1 to 20° C., 1 to 15° C., 1 to 10° C., 1.5 to 20° C., 1.5 to 15°C., 1.5 to 10° C., 2 to 20° C., 2 to 15° C., 2 to 10° C., 3 to 20° C., 3to 15° C., 4 to 20° C., 4 to 15° C., 4 to 10° C.,, 5 to 20° C., 5 to 15°C., 6 to 20° C., 6 to 15° C., 6 to 10° C., 7 to 20° C., 7 to 1.5° C., 7to 10° C., 8 to 20° C., 8 to 15° C., 8 to 10° C., 9 to 20° C., 9 to 15°C., 9 to 10° C., 10 to 15° C., typically 0 to 15° C., more typically 0to 10° C., even more typically 3° C. to 10° C., most typically 5° C. to10° C. and even most typically 5° C.

[0074] Generally the pH adjusting agent is carbon dioxide gas, carbonicacid in water, hydrated carbon dioxide in water, carbon dioxide gas inwater, carbonated soft drinks, carbonated mineral water, soda water orother carbon dioxide-containing-aqueous diluents or an alkali or anymixture thereof. Examples of alkalis are water soluble drinkable alkalissuch as sodium hydroxide, sodium carbonate, potassium carbonate orpotassium hydroxide or any mixture thereof.

[0075] Typically additions may be added during the process of theinvention or to the aqueous neutral to mildly alkaline metal bicarbonatesolution. The additives may be 0 mg or 0.5 mg to 1000 mg sodium)bicarbonate per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, typically 25 mg to 900 mg per litre of aqueousneutral to mildly alkaline metal bicarbonate solution, typically 50 mgto 800 mg or 50 mg to 500 mg per litre of aqueous neutral to mildlyalkaline metal bicarbonate solution, more typically 100 mg to 700 mg perlitre of aqueous neutral to mildly alkaline metal bicarbonate solution,even more typically 200 mg to 600 mg per litre of aqueous neutral tomildly alkaline metal bicarbonate solution, most typically 300 mg to 500mg per litre of aqueous neutral to mildly alkaline metal bicarbonatesolution, even most typically 500 mg per litre of aqueous neutral tomildly alkaline metal bicarbonate solution. The additives may also bechlorides and other appropriate salts of magnesium sodium, potassium,calcium and lithium, such as carbonates or hydroxides or sulfates, withor without the addition of sodium bicarbonate. For example, magnesiumsulfate, magnesium chloride or other soluble salts of magnesium. Furtheradditives may include potassium bicarbonate, calcium bicarbonate orlithium bicarbonate. Generally calcium bicarbonate is prepared by addingcarbonic acid or carbonated water or hydrated carbon dioxide or carbondioxide gas to a mixture of calcium carbonate in water. Generallylithium bicarbonate is prepared by adding carbonic acid and/orcarbonated water and/or hydrated carbon dioxide and/or carbon dioxidegas and/or solid carbon dioxide to a mixture of lithium carbonate inwater.

[0076] The aqueous neutral to mildly alkaline metal bicarbonate solutionmay further include a stabilising agent. The stabilising agent may alsobe a pH adjusting agent. Typically the stabilising agent is a gaseousphase, for example carbon dioxide gas, which maintains and/or stabilisesthe solution at a pH of 7 to 9 and at a temperature of 0 to 55° C. moretypically 0 to 25° C.

[0077] Generally once the solution is prepared, the solution may bestored under a blanket of carbon dioxide gas or a mixture of carbondioxide gas and a nondeleterious inert gas, for example, argon, helium,air, oxygen and/or nitrogen wherein the amount of carbon dioxide presentin the inert gas is sufficient to maintain the solution at a pH of 7 to9 and at a temperature of 0 to 25° C. and to prevent the metalbicarbonate from forming insoluble compounds which can precipitate outof solution. Typically the carbon dioxide gas above the solutionprevents loss of carbon dioxide from the solution. The amount of carbondioxide in the gaseous mixture provides partial pressure on the liquidwhich is substantially equal to the partial pressure which is producedfrom equilibrium of bicarbonate in the solution at the mixingtemperature.

[0078] Magnesium Bicarbonate Particularly

[0079] Typically the production of magnesium bicarbonate utilises thedissolution of magnesium carbonate by carbonic acid or hydrated carbondioxide solutions. Ideally, the dissolution is produced within a definedrange of conditions—a defined range of pH values, a defined range oftemperature values and a defined minimum time. For optimal biologicaland medical activities, and for therapeutic safety, the concentrationsof the component ions are defined also.

[0080] Typically to prepare the aqueous neutral to mildly alkaline metalbicarbonate solution, crushed or powdered metal carbonate, or metalcarbonate hydroxide or metal oxide, such as magnesium carbonate MgCO₃,or commercial magnesium carbonate hydroxide pentahydrate(MgCO₃)₄.Mg(OH)₂.5H₂O, or other commercial magnesium carbonatehydroxides, or hydrated magnesium oxides, or magnesium oxides heatedwith carbon dioxide, or the calcite series or dolomite series ofminerals (Mg, Ca)CO₃, or limestone or dolomite rocks is mixed withwater. A cloudy suspension is obtained. Sufficient carbonic acid and/orhydrated carbon dioxide and/or carbon dioxide gas and/or solid carbondioxide is added to obtain a solution having a pH 7 to 9 or pH 7 to 8.6,more typically pH 7.5 to 8.8 or pH 7.5 to 8.5 or pH 7.8 to 8.6, pH 7.8to 8.5, pH 7.8 to 8.4, pH 7.8 to 8.3, pH 7.8 to 8.2, pH 7.8 to 8.1, pH7.8 to 8.0, pH 7.8 to 7.9, pH 7.9 to 8.6, pH 7.9 to 8.5, pH 7.9 to 8.4,pH 7.9 to 8.3, pH 7.9 to 8.2, pH 7.0 to 8.1, pH 7.9 to 8.0, pH 8.0 to8.6, pH 8.0 to 8.5, pH 8.0 to 8.4, pH 8.0 to 8.3, pH 8.1 to 8.2, pH 8.0to 8.1, pH 8.1. to 8.6, pH 8.1 to 8.5, pH 8.1 to 8.4, pH 8.1 to 8.3, pH8.1 to 8.2, pH 8.2 to 8.6, pH 8.2 to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3,pH 8.3 to 8.6, pH 8.3 to 8.5, pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to8.5, pH 8.5 to 8.6, even more typically pH 8 to 8.6 or pH 8.2 to 8.6,most typically pH 8.3. The solution is then typically placed in a closedor sealed container at 0 to 20° C. or 0 to 15° C. with occasional mixinguntil a clear solution develops. The amount of carbonic acid and/orhydrated carbon dioxide and/or carbon dioxide gas bubbled through thesolution and dissolved therein and/or solid carbon dioxide is sufficientto prevent precipitation of water insoluble metal compounds (such asmagnesium or calcium carbonate). A clear solution is generally obtainedin about 6 hours to 7 days, typically 12 hours to 5 days, more typically24 hours to 5 days, most typically 24 hours to 3 days. Generally theaqueous neutral to mildly alkaline metal bicarbonate solution isprepared and stored at a temperature ranging from 0 to 55° C., 0 to 25°C., 0 to 20° C., 0.5 to 25° C., 0.5 to 20° C., 0.5 to 15° C., 0.5 to 10°C., 0.5 to 9° C., 0.5 to 8° C., 0.5 to 7° C., 1 to 20° C., 1 to 15° C.,1 to 10° C., 1.5 to 20° C., 1.5 to 15° C., 1.5 to 10° C., 2 to 20° C., 2to 15° C., 2 to 10° C., 3 to 20° C., 3 to 15° C., 4 to 20° C., 4 to 15°C., 4 to 10° C.,, 5 to 20° C., 5 to 15° C., 6 to 20° C., 6 to 15° C., 6to 10° C., 7 to 20° C., 7 to 15° C., 7 to 10° C., 8 to 20° C., 8 to 15°C., 8 to 10° C., 9 to 20° C., 9 to 15° C., 9 to 10° C., 10 to 15° C.,typically 0 to 15° C., more typically 0 to 10° C., even more typically3° C. to 10° C., most typically 5° C. to 10° C. and even most typically5° C. Alternatively the crushed or powdered metal carbonate, or metalcarbonate hydroxide or metal oxide or mixture thereof is added to anaqueous solution of the carbonic acid and/or hydrated carbon dioxideand/or to an aqueous solution through which carbon dioxide gas isbubbled and/or solid carbon dioxide has been added. The amount ofcarbonic acid and/or hydrated carbon dioxide and/or carbon dioxide gasbubbled through the solution and dissolved therein and/or solid carbondioxide is sufficient to prevent precipitation of water insoluble metalcompounds (such as magnesium or calcium carbonate).

[0081] Typically one litre of water is placed in a container andsufficient carbonic acid and/or carbonated water and/or hydrated carbondioxide and/or carbon dioxide gas and/or solid carbon dioxide is addedto produce a pH value of approximately pH 5.2. (In practice,approximately 40 to 45 mL of chilled (5° C.) carbonated mineral water isused depending on the initial pH of the water). The container is sealedand the contents are mixed. 485 mg magnesium carbonate hydroxidepentahydrate powder (MgCO₃)₄.Mg(OH)₂.5H₂O, molecular weight 485 isadded. The container is again sealed and the contents are mixed. Thecontainer is stored at a temperature of 0 to 10° C. and the contentsmixed regularly. Sufficient time is allowed for a clear solution ofmagnesium bicarbonate to develop at a range of pH 8.0 to pH 8.6,preferably pH 8.3. This takes approximately 24 to 72 hours.Alternatively the carbonic acid and/or carbonated water and/or hydratedcarbon dioxide and/or carbon dioxide gas and/or solid carbon dioxide isadded to the magnesium carbonate hydroxide pentahydrate powder in water.Alternatively one litre of water is placed in a container and sufficientcarbonic acid and/or carbonated water and/or hydrated carbon dioxideand/or solid carbon dioxide is added to produce a pH value less than pH5.2. (In practice, approximately 30 mL to 40 mL of chilled water is useddepending on the initial pH of the water). The container is sealed andthe contents are mixed. 485 mg magnesium carbonate hydroxidepentahydrate powder (MgCO₃)₄.Mg(OH)₂.5H₂O, molecular weight 485 isadded. The container is again sealed and the contents are mixed. Thecontainer is stored at a temperature of 0 to 10° C. and the contentsmixed regularly. The pH of the water is then adjusted with an alkalisuch as sodium hydroxide or potassium hydroxide to a pH of 8 to 8.6,typically pH 8.3. Alternatively the carbonic acid or carbonated waterand/or hydrated carbon dioxide and/or carbon dioxide gas and/or solidcarbon dioxide is added to the magnesium carbonate hydroxidepentahydrate powder in water.

[0082] The above processes may optionally be conducted under anatmosphere of carbon dioxide or a gas comprising carbon dioxide.

[0083] Generally once the solution is prepared, it may be stored under ablanket of carbon dioxide gas to maintain the solution at a pH of 7 to 9and at a temperature of 0 to 25° C. Usually one litre of the magnesiumbicarbonate solution prepared above contains approximately 120 mg ofmagnesium per litre of aqueous neutral to mildly alkaline metalbicarbonate solution and approximately 600 mg of bicarbonate. 500 mgsodium bicarbonate (or potassium bicarbonate) is added to the magnesiumbicarbonate solution and mixed. The mixture is stored in a sealedcontainer in a refrigerator. The mixture contains approximately 120 mgmagnesium per litre of aqueous neutral to mildly alkaline metalbicarbonate solution, 135 mg sodium per litre of aqueous neutral tomildly alkaline metal bicarbonate solution and 950 mg bicarbonate perlitre of aqueous neutral to mildly alkaline metal bicarbonate solution.

[0084] Generally the aqueous neutral to mildly alkaline metalbicarbonate solution of the invention is administered or consumedorally. Typically the solution is an orally drinkable solution.Typically the solution is a therapeutic orally drinkable solution.Alternatively a gelling agent may added to the solution and the solutionsubjected to gelling conditions to gel the solution and the resultantgel may be consumed orally. For example, the aqueous neutral to mildlyalkaline metal bicarbonate solution may be prepared as a solution or aniced confectionary, such as an ice block or iced dessert, which isingested orally. Alternatively the aqueous neutral to mildly alkalinemetal bicarbonate solution may be prepared in the form of a tablet,lozenge or lolly which is ingested orally. For example, the aqueousneutral to mildly alkaline metal bicarbonate solution may beadministered for metabolic acidosis or renal failure. Optionally thesolution may be sterilised. Typically the aqueous neutral to mildlyalkaline metal bicarbonate solution is prepared as a solution which isingested on a regular basis hourly, daily, monthly or yearly. The amountand frequency of aqueous neutral to mildly alkaline metal bicarbonatesolution administered/consumed in a day is generally sufficient so as tomaintain a steady bicarbonate level in the bicarbonate concentration ofa taker's body fluids. It is preferable to avoid a rapid increase in thebicarbonate level in the bicarbonate concentration of a taker's bodyfluids. The amount of aqueous neutral to mildly alkaline metalbicarbonate solution administered in a day ranges from 250 mL to 6litres, typically 250 mL to 5.5 litres, 250 mL to 5 litres, 250 mL to4.5 litres, 250 mL to 4 litres, 250 mL to 3.5 litres, 250 mL to 3litres, 500 mL to 6 litres, 500 mL to 5.5 litres, 500 mL to 5 litres,500 mL to 4.5 litres, 500 mL to 4 litres, 500 mL to 3.5 litres, 500 mLto 3 litres, more typically 1 litre to 6 litres, 1 litre to 5.5 litres,1 litre to 5 litres, 1 litre to 4.5 litres, 1 litre to 4 litres, 1 litreto 3.5 litres, even more typically 1 litre to 3 litres, 1.5 litres to 6litres, 1.5 litres to 5.5 litres, 1.5 litres to 5 litres, 1.5 litres to4.5 litres, 1.5 litres to 4 litres, 1.5 litres to 3.5 litres, 1.8 litresto 3.3 litres, 1.8 to 2.8 litres, 1.8 to 2.5 litres, 1.8 to 2.3 litres,1.8 to 2.0 litres, most typically 2 to 3 litres, typically 2.3 to 2.8litres, more typically 2.3 to 2.6 litres, usually 2.1 to 3 litres. Theaqueous neutral to mildly alkaline metal bicarbonate solution may beadministered on a full or empty stomach, typically the aqueous neutralto mildly alkaline metal bicarbonate solution is administered on anempty stomach. Usually 1.5 to 3.5 litres, typically 1.8 to 3 litres,more typically 1.5 to 2.4 litres, even more typically 1.8 to 2.1 litresand usually between 1.8 and 2.7 litres of aqueous neutral to mildlyalkaline metal bicarbonate solution is ingested, administered orconsumed on an empty stomach by a mammal (typically a human) in equal ornon equal volume amounts (100 mL-1000 mL, 200-800 mL, 250-750 mL,275-700 mL, 300-650 mL, 350-600 mL, 400-550 mL, 450-500 mL, typicallyabout 300-400 mL, more typically about 375 mL volume amounts a number oftimes (typically at set times) each day for the required number of timesper day to drink the desired daily amount of the solution). For exampleif 1800 mL per day is to be consumed then a user may drink six 300 mLamounts of the solution every 2 to 2.5 hours throughout the day. Theoral consumption of the solution three or more times at roughly equallyspaced apart intervals throughout the day is more desirable thanconsuming the solution in one or two lots throughout the day. The ideaof taking the solution is to take it regularly throughout the day sothat a simulated continuous oral intake or a close to continuous regularoral intake of the solution occurs. Thus depending on the condition andthe subject one suitable administration/consumption regime could be nineby 200 mL amounts of the solution, each 200 mL amount being orallyadministered/consumed about every 1.5-1.75 hours to provide a totaldaily intake of 1800 mL. Alternatively, once again depending on thecondition and the subject one suitable administration/consumption regimecould be nine by 300 mL amounts of the solution, each 300 mL amountbeing orally administered/consumed about every 1.5-1.75 hours to providea total daily intake of 2700 mL. Alternatively, once again depending onthe condition and the subject one suitable administration/consumptionregime could be nine by 350 mL amounts of the solution, each 350 mLamount being orally administered/consumed about every 1.5-1.75 hours toprovide a total daily intake of 3150 mL. Typically the solution isadministered/consumed 3 to 30, 3-25, 3-20, 3-15, 3-12, 3-10, 3-9, 3-8,3-7, 3-6, 3-5, 3-4, 4-30, 4-25, 4-20, 4-15, 4-12, 4-10, 4-9, 4-8, 4-7,4-6, 4-5, 5-30, 5-25, 5-20, 5-15, 5-12, 5-11, 5-10, 5-9, 5-8, 5-7, 5-6,6-30, 6-25, 6-20, 6-15, 6-12, 6-11, 6-10, 6-9, 6-8, 6-7, 7-30, 7-25,7-20, 7-15, 7-12, 7-11, 7-10, 7-9, 7-8, 8-30, 8-25, 8-20, 8-15, 8-12,8-11, 8-10, 8-9 times per day at regular or irregular intervals or amixture of both regular and irregular intervals, throughout each day.Typically the solution is administered/consumed every 0.3-10, 0.3-8,0.3-7, 0.3-6, 0.3-5, 0.3-4.5, 0.3-4, 0.3-3.5, 0.3-3, 0.3-2.5, 0.3-2,0.3-1.5, 0.3-1, 0.3-0.75, 0.3-0.5 hours/day when the subject is awake.More typically the solution is administered/consumed every 0.5-8, 0.5-7,0.5-6, 0.5-5, 0.5-4.5, 0.5-4, 0.5-3.5, 0.5-3, 0.5-2.5, 0.5-2, 0.5-1.5,0.5-1, 0.5-0.8, 0.5-0.75 hours/day when the subject is awake. Wherepossible the solution is consumed/administered on an empty (e.g. beforeeating). The solution may be administered according to these latterdosages over short (for example 1 to 60 days, 10 t

days, 3 months to 6 months, 1 day to 6 months) or long (for example 6months to 10 y

ears or more, 9 months to 18 months, 1 year to 3 years, 1 year to 5years, 2 to 6 years) period

required. Usually the amount of aqueous neutral to mildly alkaline metalbicarbonate

administered to a mammal is 5 to 100 mL per Kg, more usual 10 to 50 mLper Kg,

usual 14 to 29 mL per Kg or 25 to 43 mL per Kg.

[0085] The solution may include other additives such as sweeteners,preservatives, flavourings and other suitable additives. Examples ofsuitable sweetners include sucrose, lactose, glucose, aspartame orsaccharine. Examples of suitable flavouring agents include peppermintoil, oil of wintergreen, cherry, orange

or raspberry flavouring. Examples of suitable preservatives includesodium benzoate, vitamin E, alpha-tocopherol, ascorbic acid, methylparaben, propyl paraben or sodium bisulphite.

[0086] Typically the aqueous neutral to mildly alkaline metalbicarbonate solution is orally administered/consumed on an emptystomach. Usually consumption in this manner avoids the mixing ofbicarbonate anions with stomach acid which may result in the loss ofbicarbonate. Usually the aqueous neutral to mildly alkaline metalbicarbonate solution is consumed in small amounts a number of timesthrough a day typically at set times each day to avoid a rapid increasein the bicarbonate concentration of body fluids. Usually the amount ofaqueous neutral to mildly alkaline metal bicarbonate solution consumedat commencement is 500 mL per day and is increased by increments over aperiod of one month to the maximum consumption. This start-up schedulegenerally avoids any gastrointestinal side effects due to the smoothmuscle relaxation properties of magnesium.

[0087] The aqueous neutral to very mildly alkaline metal bicarbonatesolution of the invention may be administered intraveniously (e.g. bydiscrete injection, semi continuous injection or drip feed or continuousinjection or drip feed) or by other parenteral routes. Anotherembodiment of the invention is directed to a pharmaceutical compositioncomprising the solution of the first or eleventh embodiments togetherwith one or more pharmaceutically acceptable carriers, diluents,adjuvants and/or excipients. Typically the pharmaceutical composition issuitable for oral or parenteral administration. Another embodiment ofthe invention is directed to a veterinary composition comprising thesolution of the first or eleventh embodiments together with one or moreveterinarily acceptable carriers, diluents, adjuvants and/or excipients.Typically the veterinary composition is suitable for oral or parenteraladministration. The amount and frequency of aqueous neutral to mildlyalkaline metal bicarbonate solution administered/consumed in a day isgenerally sufficient so as to maintain a steady bicarbonate level in thebicarbonate concentration of a taker's body fluids. It is preferable toavoid a rapid increase in the bicarbonate level in the bicarbonateconcentration of a taker's body fluids. For parenteral administration,the solution is generally sterile. Suitable mono-toxic parenterallyacceptable diluents or solvents include water, Ringer's solution,isotonic salt solution, 1,3-butanediol, ethanol, propylene glycol orpolyethylene glycols in mixtures with water. Aqueous solutions orsuspensions may further comprise one or more buffering agents. Suitablebuffering agents include sodium borate, sodium acetate, sodium citrate,or sodium tartrate, for example. Typically the solution is administeredon a regular basis throughout a day to a patient requiring treatment.For example a patient may be parenterally administered the solution byway of a continuous drip feed or alternatively by way of a number ofinjections of the solution throughout a day (e.g. every 0.5-8 hours,more typically every 1-4 hours). The treatment is generally continued aslong as required to alleviate the patient's symptoms to a satisfactorylevel. For concentration of metal bicarbonate in the compositions,frequency of administration and amount administered see discussion underoral administration.

BRIEF DESCRIPTION OF DRAWINGS

[0088]FIG. 1 are plots of the survival curves for a control group ofsheep and a treatment group of sheep;

[0089]FIG. 2 is a photograph showing osteoarthritis in the joints of thefingers and thumb. Osteoarthritis before the consumption of aqueousmetal bicarbonate solution. Note the swelling and ‘claw-like’ handresulting from joint flexion and joint displacement. (The patient waspushing down with her hand ‘as hard as possible’ in an attempt to placeher hand flat on the underlying surface.); and

[0090]FIG. 3 is a photograph showing osteoarthritis in the joints of thefingers and thumb. Osteoarthritis twelve months after commencement ofthe consumption of aqueous metal bicarbonate solution. Note that thefingers can be extended and the joints are ‘straighter’ than twelvemonths previously. (The patient bad placed her hand flat on theunderlying surface without exerting any force.)

BEST MODE AND OTHER MODE(S) FOR CARRYING OUT THE INVENTION

[0091] Magnesium bicarbonate is a natural hydrated salt which existsonly in an aqueous solution. It may be formed in spring water by an ionexchange process between the protons in carbonic acid (formed from thehydration of carbon dioxide located in the atmosphere, organic material,soils and rocks) and the magnesium in the constituent minerals of rocks(particularly the ferromagnesian minerals known as pyroxene and olivinethat constitute basalt rocks).

[0092] The ion exchange process can be represented by the followingequations:

[0093] The term magnesium bicarbonate is used universally to describethe mixture of magnesium cations and bicarbonate anions found in springwaters and mineral waters. Most spring waters and mineral waters haveacidic pH values (about pH 6.0). If the pH value of the water rises (dueto contact with hydroxides), the magnesium cations and bicarbonateanions “attract” each other (reversibly) to form the true salt. Thechemical formula of magnesium bicarbonate may be written as Mg(HCO₃)₂,or (more accurately) Mg(H₂O)₄(HCO₃)₂. This latter formula takes intoaccount the hexahydrated magnesium cation Mg(H₂O)₆ ²⁺.

[0094] In essence, magnesium bicarbonate exists in aqueous solutionprobably as an hydrated salt of indeterminate hydration size due to thehydrogen bonds between linked water dipoles centred around the hydratedmagnesium cation.

[0095] The chemical processes occurring in magnesium bicarbonatesolutions are complex and depend on the concentrations of magnesiumcations and other ions. The following reactions are considered to occur:

[0096] There exists also a range of possible acid-base equilibriainvolving HCO₃ ⁻, H₃O⁺, CO₃ ²⁻ and OH⁻ ions and CO₂ and H₂CO₃. Usuallythe pH adjusting agent (and/or stabilising agent) maintains theacid-base equilibria.

[0097] Typically to prepare the aqueous neutral to mildly alkaline metalbicarbonate solution, crushed or powdered metal carbonate, or metalcarbonate hydroxide or metal oxide, such as magnesium carbonate MgCO₃,or commercial magnesium carbonate hydroxide pentahydrate(MgCO₃)₄.Mg(OH)₂.5H₂O, or other commercial magnesium carbonatehydroxides, or hydrated magnesium oxides, or magnesium oxides heatedwith carbon dioxide, or the calcite series or dolonite series ofminerals (Mg, Ca)CO₃, or limestone or dolomite rocks is mixed withwater. A cloudy suspension is obtained. Sufficient carbonic acid orhydrated carbon dioxide or carbon dioxide gas is added to obtain asolution having a pH 7 to 9 or pH 7 to 8.6, more typically pH 7.5 to 8.8or pH 7.5 to 8.5 or pH 7.8 to 8.6, pH 7.8 to 8.5, pH 7.8 to 8.4, pH 7.8to 8.3, pH 7.8 to 8.2, pH 7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to 7.9, pH7.9 to 8.6, pH 7.9 to 8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH 7.9 to 8.2,pH 7.9 to 8.1, pH 7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH 8.0 to8.4, pH 8.0 to 8.3, pH 8.0 to 8.2, pH 8.0 to 8.1, pH 8.1 to 8.6, pH 8.1to 8.5, pH 8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH 8.2 to 8.6, pH8.2 to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to 8.6, pH 8.3 to 8.5,pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH 8.5 to 8.6, even moretypically pH 8 to 8.5 or pH 8.2 to 8.6, most typically pH 8.3. Thesolution is then typically placed in a sealed container at 0 to 20° C.with occasional mixing until a clear solution develops. A clear solutionis generally obtained in about 6 hours to 7 days, typically 12 hours to5 days, more typically 24 hours to 5 days, most typically 24 hours to 3days. Generally the aqueous neutral to mildly alkaline metal bicarbonatesolution is prepared and stored at a temperature ranging from 0 to 25°C., 0 to 20° C., 0.5 to 25° C., 0.5 to 20° C., 0.5 to 15° C., 0.5 to 10°C., 0.5 to 9° C., 0.5 to 8° C., 0.5 to 7° C., 1 to 20° C., 1 to 15° C.,1 to 10° C., 1.5 to 20° C., 1.5 to 15° C., 1.5 to 10° C., 2 to 20° C., 2to 15° C., 2 to 10° C., 3 to 20° C., 3 to 15° C., 4 to 20° C., 4 to 15°C., 4 to 10° C., 5 to 20° C., 5 to 15° C., 6 to 20° C., 6 to 15° C., 6to 10° C., 7 to 20° C., 7 to 15° C., 7 to 10° C., 8 to 20° C., 8 to 15°C., 8 to 10° C., 9 to 20° C., 9 to 15° C., 9 to 10° C., 0 to 15° C.,typically 0 to 15° C., more typically 0 to 10° C., even more typically3° C. to 10° C., most typically 5° C. to 10° C. and even most typically5° C. Alternatively the crushed or powdered metal carbonate, or metalcarbonate hydroxide or metal oxide or mixture thereof is added to anaqueous solution of the carbonic acid or hydrated carbon dioxide orcarbon dioxide gas.

[0098] Typically one litre of water is placed in a container andsufficient carbonic acid or carbonated water or hydrated carbon dioxideor carbon dioxide gas is added to produce a pH value of approximately pH5.2. (In practice, approximately 40 to 45 mL of chilled (5° C.)carbonated mineral water is used depending on the initial pH of thewater). The container is sealed and the contents are mixed. 485 mgmagnesium carbonate hydroxide pentahydrate powder (MgCO₃)₄.Mg(OH)₂.5H₂O,molecular weight 485 is added. The container is again sealed and thecontents are mixed. The container is stored at a temperature of 0 to 10°C. and the contents mixed regularly. Sufficient time is allowed for aclear solution of magnesium bicarbonate to develop at a range of pH 8.0to pH 8.5, typically pH 8.3. This takes approximately 24 to 72 hours.Alternatively the carbonic acid or carbonated water or hydrated carbondioxide or carbon dioxide gas is added to the magnesium carbonatehydroxide pentahydrate powder in water.

[0099] Alternatively one litre of water is placed in a container andsufficient carbonic acid or carbonated water or hydrated carbon dioxidegas is added to produce a pH value less than pH 5.2. (In practice,approximately 30 mL to 40 mL of chilled water is used depending on theinitial pH of the water). The container is sealed and the contents aremixed. 485 mg magnesium carbonate hydroxide pentahydrate powder(MgCO₃)₄.Mg(OH)₂.5H₂O, molecular weight 485 is added. The container isagain sealed and the contents are mixed. The container is stored at atemperature of 0 to 10° C. and the contents mixed regularly. The pH ofthe water is then adjusted with an alkali such as sodium hydroxide orpotassium hydroxide to a pH of 8 to 8.5, typically pH 8.3. Alternativelythe carbonic acid or carbonated water or hydrated carbon dioxide orcarbon dioxide gas is added to the magnesium carbonate hydroxidepentahydrate powder in water.

[0100] Generally once the solution is prepared, the solution may bestored in a closed container under a blanket of carbon dioxide gas or amixture of carbon dioxide gas and usually a nondeleterious inert gas,for example, argon, helium and/or nitrogen to maintain the solution at apH of 7 to 9 and at a temperature of 0 to 25° C. and at 0.8 to 5 atm.The carbon dioxide gas blanket prevents loss of carbon dioxide from thesolution. The amount of carbon dioxide in the gaseous mixture providespartial pressure on the liquid which is substantially equal to thepartial pressure of carbon dioxide from carbon dioxide from the solutionwhich is produced from equilibrium of bicarbonate in the solution at theparticular temperature. In this way the solution is stabilised. If thesolution were left in an open container for any substantial length oftime precipitation of metal carbonate from the solution would occur as aresult of decomposition of the bicarbonate in the solution as carbondioxide is liberated from the solution. By using a stabilising agent inand/or above the solution such decomposition is substantially minimisedor prevented. Alternatively the solution may be stored in a closed orsealed container (generally airtight) which is substantially filled withthe solution whereby there is substantially no gas in the container orlittle gas compared to the amount of liquid in the container.

[0101] The relevant chemical reactions may be represented by thefollowing equations:

[0102] Usually one litre of the magnesium bicarbonate solution preparedabove contains approximately 120 mg of magnesium per litre of aqueousneutral to mildly alkaline metal bicarbonate solution and approximately600 mg of bicarbonate. 500 mg sodium bicarbonate (or potassiumbicarbonate) is added to the magnesium bicarbonate solution and mixed.The mixture is stored in a sealed container in a refrigerator. Themixture contains approximately 120 mg magnesium per litre of aqueousneutral to mildly alkaline metal bicarbonate solution, 135 mg sodium perlitre of aqueous neutral to mildly alkaline metal bicarbonate solutionand 950 mg bicarbonate per litre of aqueous neutral to mildly alkalinemetal bicarbonate solution.

[0103] In the body, normal intracellular pH value is pH 7.2. Underacidic conditions, such as adenosine triphosphate (ATP) hydrolysis,intracellular pH value may decrease to pH 6.5. In practice, a pH valueis chosen for bicarbonate solutions that exceeds normal blood plasma pHvalue (pH>7.38).

[0104] A low temperature, between 0 and 10° C., typically 5 to 10° C.,ensures that carbon dioxide stays dissolved in solution to maximisecarbon dioxide hydration Above 15 to 20° C., the solubility of carbondioxide is low, the carbon dioxide leaves the solution, and particlesand sediments may occur in the solution. Above 15 to 20° C., thesolution may be cloudy in appearance.

[0105] At high magnesium concentrations, a minimum time, at least 24 to72 hours at 5° C., is required for completion of the kinetic processesthat produce a clear solution of magnesium bicarbonate. (The kineticprocesses include the hydration of carbon dioxide, the dissolution ofmagnesium carbonate and the dissolution of magnesium hydroxide.)

[0106] The concentration of magnesium cations (in association withbicarbonate anions) is generally in the range 25 mg to 250 mg per litreaqueous neutral to mildly alkaline metal bicarbonate solution (dependingon the pH value of the metal bicarbonate solution). Usually the maximummagnesium concentration that can be maintained in solution as magnesiumbicarbonate may be approximately 120 mg per litre aqueous neutral tomildly alkaline metal bicarbonate solution at pH 8.3. As the pH valuedecreases, the concentration of magnesium that can be maintained insolution increases. Because magnesium chloride is soluble, higherconcentrations of magnesium can be maintained in solution if chlorides(such as sodium chloride) are added to the aqueous neutral to mildlyalkaline metal bicarbonate solution.

[0107] The solubility product constant for magnesium carbonate isreported to be approximately 3.5×10⁻⁸. The solubility product constantfor magnesium hydroxide is reported to be approximately 1.1×10⁻¹¹.Calculated from these values, the maximum concentrations of magnesiumcations that can exist in solution as carbonates or hydroxides areapproximately 20 mg per litre aqueous metal bicarbonate solution and 10mg per litre aqueous neutral to mildly alkaline metal bicarbonatesolution respectively.

[0108] Generally the aqueous neutral to mildly alkaline metalbicarbonate solution of the invention is administered or consumedorally. Typically the solution is an orally drinkable solution.Typically the solution is a therapeutic orally drinkable solution. Forexample, the aqueous neutral to mildly alkaline metal bicarbonatesolution may be prepared as a solution or an iced confectionary, such asan ice block or iced dessert, which is ingested orally. Alternativelythe aqueous neutral to mildly alkaline metal bicarbonate solution may beprepared in the form of a tablet, lozenge or lolly which is ingestedorally. For example, the aqueous neutral to mildly alkaline metalbicarbonate solution may be administered for metabolic acidosis or renalfailure. Optionally the solution may be sterilised. Typically theaqueous neutral to mildly alkaline metal bicarbonate solution isprepared as a solution which is ingested hourly, daily, monthly oryearly. The amount of aqueous neutral to mildly alkaline metalbicarbonate solution administered in a day ranges from 250 mL to 6litres, typically 250 mL to 5.5 litres, 250 mL to 5 litres, 250 mL, to4.5 litres, 250 mL to 4 litres, 250 mL to 3.5 litres, 250 mL to 3litres, 500 mL to 6 litres, 500 mL to 5.5 litres, 500 mL to 5 litres,500 mL to 4.5 litres, 500 mL to 4 litres, 500 mL to 3.5 litres, 500 mLto 3 litres, more typically 1 litre to 6 litres, 1 litre to 5.5 litres,1 litre to 5 litres, 1 litre to 4.5 litres, 1 litre to 4 litres, 1 litreto 3.5 litres, even more typically 1 litre to 3 litres, 1.5 litres to 6litres, 1.5 litres to 5.5 litres, 1.5 litres to 5 litres, 1.5 litres to4.5 litres, 1.5 litres to 4 litres, 1.5 litres to 3.5 litres, mosttypically 2 to 3 litres, usually 2.1 to 3 litres. The aqueous neutral tomildly alkaline metal bicarbonate solution may be administered on a fullor empty stomach, typically the aqueous neutral to mildly alkaline metalbicarbonate solution is administered on an empty stomach. Usually 1.5 to3 litres, more typically 1.5 to 2.4 litres, even more typically 1.8 to2.1 litres and usually between 1.8 and 2.7 litres of aqueous neutral tomildly alkaline metal bicarbonate solution is ingested on an emptystomach in approximately 300 mL volumes at set times each day. Thesolution may be administered according to these latter dosages overshort (for example 1 to 10 days) or long (for example 6 months to 10years or more) periods as required. Usually the amount of aqueousneutral to mildly alkaline metal bicarbonate solution administered to amammal is 5 to 100 mL per Kg, more usual 10 to 50 mL per Kg, most usual14 to 29 mL per Kg or 25 to 43 mL per Kg.

[0109] Typically the aqueous neutral to mildly alkaline metalbicarbonate solution is consumed on an empty stomach. Usuallyconsumption in this manner avoids the mixing of bicarbonate anions withstomach acid which may result in the loss of bicarbonate. Usually theaqueous neutral to mildly alkaline metal bicarbonate solution isconsumed in small amounts at set times each day to avoid a rapidincrease in the bicarbonate concentration of body fluids. Usually theamount of aqueous neutral to mildly alkaline metal bicarbonate solutionconsumed at commencement is 500 mL per day and is increased byincrements over a period of one month to the maximum consumption. Thisstart-up schedule generally avoids any gastrointestinal side effects dueto the smooth muscle relaxation properties of magnesium.

[0110] The advantages of the aqueous neutral to mildly alkaline metalbicarbonate solution of the invention are that the magnesium cationsfunction as bicarbonate transporters into body cells. Magnesiumbicarbonate enters body cells and the bicarbonate anions function todisplace from equilibrium the dissociation reaction of intracellularcarbonic acid. Magnesium bicarbonate enters body cells and thebicarbonate anions function as an intracellular proton sink (or protonscavenger). These reactions can be represented by the one equation

[0111] Magnesium bicarbonate enters body cells and the bicarbonateanions function to displace from equilibrium the hydration reaction ofcarbon dioxide which is catalysed by the enzyme carbonic anhydrase. Thisreaction can be represented by the equation

[0112] Usually appropriate salts of magnesium, sodium, potassium,calcium and lithium should not exceed the concentrations of thecomponent elements recommended by health authorities. The concentrationsof component elements cannot exceed concentrations restricted by thesolubility product constants of respective hydroxides and carbonates.

EXAMPLE 1 An Experiment to Decrease Intracellular Proton Concentrationsand to Increase Intracellular Bicarbonate Concentrations in MammalianCells In Vitro

[0113] Aqueous bicarbonate anions act as proton sinks in the presence ofexcess proton concentrations in solution. This reaction can berepresented by the chemical equation

[0114] In the presence of sufficient concentrations of bicarbonateanions, the reaction is essentially complete and proton concentrationsdecrease. The pH value of the solution increases. When plasmabicarbonate anions are present outside mammalian body cells insufficient concentrations, they are translocated into the cytoplasm ofthe cells across the cell plasma membranes. Indeed bicarbonate anionsequilibrate rapidly across mammalian cell membranes. Bicarbonatetranslocation into cells takes place via several processes. Theseprocesses include a chloride-bicarbonate anion exchange and a sodiumdependent chloride-bicarbonate anion exchange and potassium co-transportand magnesium co-transport.

[0115] An experiment was conducted to decrease intracellular protonconcentrations and to increase intracellular bicarbonate concentrationsin mammalian body cells in vitro. Throughout the experiment,extracellular pH determinations were made using a pH electrode andintracellular pH determinations were made using a trapped fluoresceinderivative. An increase in intracellular proton concentrations(intracellular acidification) was achieved by applying 10 mmol ammoniumchloride (NH₄Cl) solution to a suspension of cells and then removing theNH₄Cl. An increase in intracellular bicarbonate concentrations wasachieved by applying an aqueous metal bicarbonate solution to asuspension of cells. The aqueous metal bicarbonate solution containedapproximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre and HCO₃ ⁻ 950mg per litre at pH 8.3. This aqueous metal bicarbonate solution wasequivalent to 15 mmol bicarbonate approximately. Blood was collected insodium heparin from a range of mammals and the leucocytes removed. Theleucocytes were washed and re-suspended in isotonic saline.Intracellular pH determinations were made by loading leucocytes for 15minutes with (10 micromol in saline)2,7-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). Cells wereilluminated at 440 nm and 490 nm and fluorescence was measured at 530nm.

[0116] The experiment utilising sheep leucocytes is given stepwisebelow:

[0117] Step 1. Increase in intracellular proton concentrations(cytoplasmic acidification)

[0118] A. Leucocytes suspended in normal saline after pretreatment withfluorescein.

[0119] Extracellular pH 7.2

[0120] Intracellular pH 7.1

[0121] B. 10 mmol ammonium chloride (NH₄Cl) solution pH 7.5 applied tosuspension of leucocytes for 10 minutes.

[0122] C. Leucocytes washed and re-suspended in normal saline.

[0123] Extracellular pH 7.3

[0124] Intracellular pH 6.1

[0125] Result: Cells have increased intracellular proton concentrations.Cytoplasm is acidified.

[0126] Step 2. Decrease in intracellular proton concentrations

[0127] A. Acidified leucocytes (from Step 1.) divided into two groups;Control group and Treatment group.

[0128] B. Treatment group of leucocytes exposed to aqueous metalbicarbonate solution.

[0129] After 3 minutes:

[0130] Extracellular pH 7.5

[0131] Intracellular pH 7.0

[0132] C. Control group of leucocytes not exposed to aqueous metalbicarbonate solution.

[0133] After 5 minutes:

[0134] Extracellular pH 7.2

[0135] Intracellular pH 6.6

[0136] Result: Cells treated with aqueous metal bicarbonate solutionrapidly decrease intracellular proton concentrations. Cytoplasm showsrapid recovery from acidification relative to non-treated cells.

[0137] Step 3. Increase in intracellular bicarbonate concentrations

[0138] A. Leucocytes suspended in normal saline after pretreatment withfluorescein.

[0139] Extracellular pH 7.2

[0140] Intracellular pH 7.1

[0141] B. Aqueous metal bicarbonate solution applied to suspension ofleucocytes for 20 minutes.

[0142] Extracellular pH 7.9

[0143] Intracellular pH 7.4

[0144] Result: Cells treated with aqueous metal bicarbonate solutionhave increased intracellular bicarbonate concentrations which aremanifested by an increase in pH value of cytoplasm.

[0145] The experiment was repeated with leucocytes from mice, rats,guinea pigs, cattle, horses, dogs, cats and humans. In all cases,acidified cells treated with aqueous metal bicarbonate solution haddecreased intracellular proton concentrations. In all cases, cellstreated with aqueous metal bicarbonate solution had increasedintracellular bicarbonate concentrations which were manifested byincreased pH values of cytoplasm.

[0146] The experiment was repeated with aqueous metal bicarbonatesolutions that contained a range of concentrations of Mg²⁺, Na⁺, HCO₃ ⁻and K⁺ and Ca²⁺ ions. Significant results were obtained for thefollowing range of concentrations: Range of concentrations to achieveIon significant results Mg²⁺ 20 to 120 mg/litre Na⁺ 50 to 500 mg/litreK⁺ 50 to 500 mg/litre Ca²⁺ 20 to 150 mg/litre HCO₃ ⁻ 250 to 2,100mg/litre   (HCO₃ ⁻) (4 mmol to 35 mmol)

[0147] Significant results were obtained for pH range pH 7.5 to 9.5. (pH9.5 was achieved by the addition of NaOH).

[0148] Aqueous metal bicarbonate solutions, containing a range of cationand bicarbonate anion concentrations, decrease intracellular protonconcentrations and increase intracellular bicarbonate concentrations inmammalian cells in vitro.

EXAMPLE 2 An Experiment to Demonstrate Bicarbonate Anion TranslocationFrom Aqueous Metal Bicarbonate Solution Into the Mammalian Body Againsta Bicarbonate Anion Concentration Gradient

[0149] Mammalian plasma contains bicarbonate anions at a concentrationabout 25 mmol (HCO₃ ⁻ 1,500 mg per litre). When ingested, aqueous metalbicarbonate solution produces biochemical, physiological and medicaleffects at bicarbonate anion concentrations about 16 mmol (HCO₃ ⁻ 950 mgper litre). Aqueous metal bicarbonate solution, at bicarbonate anionconcentration about 16 mmol, contains two thirds the bicarbonate anionconcentration of plasma, so bicarbonate anions must be translocated intothe mammalian body against a bicarbonate anion concentration gradient.

[0150] Mammalian plasma contains cations at concentrations around Mg² ⁺24 mg per litre, Na⁺ 3,300 mg per litre, K⁺ 175 mg per litre and Ca²⁺100 mg per litre. Aqueous metal bicarbonate solution commonly containscations at concentrations around Mg²⁺ 120 mg per litre, Na⁺ 13.5 mg perlitre, K⁺ 100 mg per litre and Ca²⁺ 20 mg per litre. Aqueous metalbicarbonate solution commonly contains 5 times the magnesium cationconcentration of plasma. Other cations are present commonly in aqueousmetal bicarbonate solution in concentrations lower than plasma.

[0151] The concentrations in cations and anions in plasma can becompared with concentrations of cations and anions in aqueous metalbicarbonate solution by examination of the following table:Concentrations of cations and anions Aqueous metal Ion Plasmabicarbonate solution Cl⁻ 3,600 mg/litre 0 mg/litre Na⁺ 3,300 mg/litre135 mg/litre HCO₃ ⁻ 1,500 mg/litre 950 mg/litre K⁺ 175 mg/litre 100mg/litre Ca²⁺ 100 mg/litre 20 mg/litre Mg²⁺ 24 mg/litre 120 mg/litre

[0152] It is suggested that sodium cations and chloride anions leaveplasma along their respective concentration gradients and magnesium andbicarbonate ions enter plasma along a magnesium cation concentrationgradient. Magnesium functions as a bicarbonate transporter. In addition,it is suggested that bicarbonate anions enter plasma bychloride-bicarbonate exchange processes along a chloride anionconcentration gradient (chloride ‘out’, bicarbonate ‘in’).

[0153] In mammals, any large increases in plasma bicarbonateconcentrations can be decreased normally by a number of biochemical andphysiological homeostatic control processes. These processes occur intime frames that range from minutes to hours and longer. One of the maincontrol processes that occurs as a result of increased plasmabicarbonate concentration is an alteration in bicarbonate chemistry inthe kidneys. This is manifested by a decrease in proton concentration inurine and by a pH value of urine that is less acidic. In the presence ofincreased plasma bicarbonate, kidney tubule cells decrease theirexcretion of protons. Kidney control of bicarbonate concentration is notinstantaneous and occurs within a time frame of several hours to severaldays. Unless a mammal has physiological or clinical acidosis, it isdifficult to detect small increases in plasma bicarbonate concentration.Any increases in plasma bicarbonate concentration are taken up by bodycells. Indeed, plasma bicarbonate equilibrates with intracellularbicarbonate rapidly In a normal mammal, a measurable increase in plasmabicarbonate concentration occurs only during an artificially inducedalkalosis and is detectable either when the consumption of bicarbonateanions (as NaHCO₃) greatly exceeds the concentration of bicarbonate innormal plasma or when bicarbonate anions (as NaHCO₃) are administeredintravenously.

[0154] An experiment was conducted to determine if bicarbonate anions inaqueous metal bicarbonate solutions are translocated against abicarbonate concentration gradient into the body. Bicarbonatetranslocation against a concentration gradient could occur either viaenergy (ATP) dependent processes or via anion (chloride-bicarbonate)exchange or via co-transport with cations along cation concentrationgradients. There are also complex thermodynamic processes involvingintracellular and extracellular concentrations of bicarbonate anions,hydroxide anions, protons and carbon dioxide that may assist in theoverall translocation of bicarbonate anions. These processes ofteninvolve the production of bicarbonate anions by carbonic anhydraseenzymes. In the experiment, entry of bicarbonate anions into the bodywas assessed by determinations of proton concentration in urine; thatis, the pH value of urine.

[0155] Ten people had urine pH value

ssed once per week for 3 months. Urine pH values were assessed once perweek for a further 3 months after commencement of consumption of aqueousmetal bicarbonate solution. The aqueous metal bicarbonate solutioncontained approximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre andHCO₃ ⁻ 950 mg per litre. The major component of the solution wasmagnesium bicarbonate Mg(HCO₃)₂ 720 mg per litre approximately. Resultsare given below: Mean pH value of urine (Early morning sample) Prior toconsumption of aqueous pH 5.9 metal bicarbonate solution: Aftercommencement of consumption pH 6.7 of aqueous metal bicarbonatesolution:

[0156] The consumption of aqueous metal bicarbonate solution decreasesproton excretion by the kidneys. The pH value of urine increases.

[0157] These results demonstrate that bicarbonate anions from aqueousmetal bicarbonate solution are translocated against a bicarbonate anionconcentration gradient into the body. This may occur either viaco-transport with cations along a cation concentration gradient or viachloride-bicarbonate exchange processes along a chloride anionconcentration gradient (chloride ‘out’, bicarbonate ‘in’). In the caseof aqueous metal bicarbonate solution, the only cation concentrationgradient possible is that involving magnesium cation concentrations.

[0158] The consumption of aqueous metal bicarbonate solution leads to anincrease in bicarbonate anion concentration in the body which ismanifested by a decrease in proton concentration in urine; an increasein pH value of urine.

EXAMPLE 3 An Experiment to Improve the Buffering Capacities of theExtracellular and Intracellular Bicarbonate Buffers and to DecreaseSenescence and to Increase Longevity in a Representative Mammal

[0159] Mammalian body cells produce continuously concentrations ofcarbon dioxide. Upon hydration, carbon dioxide increases protonconcentrations in the cytoplasm of body cells. The pH values of thecytoplasm of body cells are lowered. The production of protons incytoplasm by the hydration of carbon dioxide can be represented by thefollowing chemical equations:

CO₂+H₂O

H₂CO₃

H₂CO₃+H₂O

H₃O⁺+HCO₃ ⁻

[0160] The protons produced the cytoplasm of body cells by the hydrationof carbon dioxide, and other intracellular reactions, are bufferednormally by intracellular bicarbonate buffers. The bicarbonate anions inintracellular buffers derive manly from the extracellular bicarbonate ofblood plasma. The bicarbonate anions in blood plasma originate fromerythrocytes as products of erythrocyte carbonic anhydrase enzymereactions.

[0161] When plasma bicarbonate anions are present outside mammalian bodycells in sufficient concentrations, they are translocated into thecytoplasm of the cells across the cell plasma membranes. Indeed, plasmabicarbonate equilibrates with cytoplasmic bicarbonate rapidly.Bicarbonate translocation into cells takes place via several processes.These processes include a chloride-bicarbonate anion exchange and asodium dependent chloride-bicarbonate anion exchange and potassiumco-transport and magnesium co-transport. There are also complexthermodynamic processes involving intracellular and extracellularconcentrations of bicarbonate anions, hydroxide ions, protons and carbondioxide that may assist in the overall translocation of bicarbonateanions. These processes often involve the production of bicarbonateanions by carbonic anhydrase enzymes.

[0162] Concentrations of bicarbonate anions that are translocated intomammalian body cells improve the buffering capacity of the cytoplasm ofthe cells. Concentrations of bicarbonate anions and concentrations ofcarbon dioxide form a buffer system described by theHenderson-Hasselbalch equation:

pH=pK+log ([HCO₃ ⁻]/[H₂CO₃])

[0163] (Where pK is the pK of hydrated carbon dioxide H₂CO₃ and has anapproximate numerical value of 6.35)

[0164] For a classical (closed system) buffer to be effective, the ratioof the conjugate base to the acid (in the above case [HCO₃ ⁻]/[H₂CO₃])must be between 0.1 and 10. This ratio applies also to buffers inbiological (open) systems. In mammalian body cells, the continuous andopen production of carbon dioxide means that continuous supplies ofbicarbonate anions are required to maintain effective and optimalbuffering capacities. Under conditions of excess proton concentrations,from carbon dioxide production and ATP hydrolysis and other metabolicprocesses, the supply of bicarbonate fails and the effective and optimalbuffering capacities of mammalian body cells falter.

[0165] The vitality of mammalian body cells is linked critically to thebuffering capacities of the extracellular fluids and the cytoplasm ofthe cells. Processes of cellular degeneration occur when bufferingcapacities falter in the presence of excess proton concentrations.Cellular degenerations are manifested in the mammalian body bydegenerative diseases and senescence. Examples of degenerative diseasesin mammals that are linked casually to extracellular and intracellularproton concentrations include osteoporosis, osteoarthritis, the diseasesassociated with chronic inflammation, the diseases associated withlysosomal enzyme activities, the diseases associated with oxidations ofcell nucleic acids, cell protein amino acids and cell membrane lipids,and the diseases associated with aberrations of mitochondrialrespiration.

[0166] An experiment was conducted to improve the buffering capacitiesof the extracellular and intracellular bicarbonate buffers and toconsequently decrease senescence and increase longevity in arepresentative mammal. One hundred and ten Merino ewe lambs were dividedrandomly at weaning into a control group and a treatment group. Thegroups were of equal size and were maintained under similar conditionsexcept for the pH values and aqueous metal bicarbonate concentrations ofdrinking water supplies. Sheep were selected as the representativemammal because their life span and body weight are more representativeof typical mammals than laboratory rodents, their life span is notexcessively long, their body size permits multiple blood and tissuesample collections, they are easy to handle and their husbandry issuited to experimental conditions. The control group was maintained, forthe full life span of the sheep, in small experimental paddocks withslightly acidic (less than pH 6.5) drinking water supplies thatcontained bicarbonate concentrations less than 30 mg per litre. Thetreatment group was maintained, for the full life span of the sheep, insmall experimental paddocks with slightly alkaline (pH 7.8 to 9.0)drinking water supplies that contained bicarbonate concentrationsbetween 300 mg per litre and 800 mg per litre. The drinking watersupplies for the treatment group were loaded with the appropriateconcentrations of bicarbonate anions by the addition of crushed andpowdered magnesite MgCO₃ to the water. The magnesite frequentlycontained calcite CaCO₃ and dolomite (Ca,Mg)CO₃. The magnesite wasdissolved in the drinking water either with the assistance of commercialsupplies of carbon dioxide gas or carbonic acid or with local suppliesof hydrated carbon dioxide. This dissolution process can be representedby the following chemical equations:

CO₂+H₂O

H₂CO₃

H₂CO₃+H₂O

H₃O⁺+HCO₃ ⁻

MgCO₃+H₃O⁺+HCO₃ ⁻

Mg(HCO₃)₂+H₂O

[0167] The treatment group of sheep consumed slightly alkaline (pH 7.8to 9.0) drinking water that contained bicarbonate concentrations between300 mg per litre and 800 mg per litre. At this pH value, and thisbicarbonate concentration, bicarbonate was mostly in the form ofmagnesium bicarbonate Mg(HCO₃)₂:

[0168] In addition, some sediments of carbonate (Ca,Mg)CO₃ were presentin the drinking water during summer months:

[0169] The mean pH values and the mean magnesium, calcium andbicarbonate concentrations in the drinking water supplies are givenbelow (the concentrations of cations and bicarbonate anions were notstoichiometric in the drinking water—particularly the drinking water ofthe control group—because of the presence of some concentrations ofsulphate, chloride and sodium ions): Means of parameters in drinkingwater Control Group Treatment Group pH 6.1 8.4 Mg²⁺ mg/litre 13 110 Ca²⁺mg/litre 20 30 HCO₃ ⁻ mg/litre 25 660

[0170] In the late stages of pregnancy, there is a tendency for pregnantmammals to become hypoglycaemic and hyperketonaemic. Hyperketonaemiasubjects the pregnant mammal to an acid load (increase in protonconcentrations). This acid load may result in clinical acidosis. Likeall mammals, pregnant ewes tend to be hypoglycaemic and hyperketonaemiclate in pregnancy. In ewes affected clinically with acidosis,bicarbonate concentrations range between 14 to 20 mmol per litre plasma.

[0171] Over several years, plasma bicarbonate concentrations weredetermined for the control group and the treatment group one week priorto lambing. Determination of plasma bicarbonate concentrations prior tolambing is a direct measure of extracellular and intracellularbicarbonate buffering capacity. In ewes with effective extracellular andintracellular bicarbonate buffers, bicarbonate concentrations aremaintained in a range between 24 to 27 mmol per litre plasma. Plasmabicarbonate concentrations are given below: Mean plasma bicarbonateconcentrations one week prior to lambing (mmol per litre) Age (years)Control Group Treatment Group 4 24.9 26.1 6 22.8 25.9 8 22.2 26.4 1021.9 25.8

[0172] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, improves the bufferingcapacities of extracellular and intracellular bicarbonate buffers inmammals.

[0173] In mammalian demography, there are two measurements utilisedcommonly in the experimental study of degenerative diseases andsenescence. The first measurement is called fifty percent survival.Fifty percent survival describes the chronological age at which half anoriginal population bas died. The second measurement is called maximumlife span. Maximum life span describes the age of the longest livedsurvivors of a population. The fifty percent survival measurement isconsidered to reflect susceptibility to accidents and infectious anddegenerative diseases in mammals. The maximum life span measurement isconsidered to reflect the innate processes of senescence in mammals. Thefifty percent survival measurement and the maximum life span measurementfor the control group and the treatment group are given below: Fiftypercent survival Control group 8 years Treatment group 11 years Maximumlife span Control group 13 years Treatment group 17 years

[0174] The treatment group had a larger fifty percent survivalmeasurement and a larger maximum life span measurement than the controlgroup.

[0175] The death of each member of a population of mammals can beplotted graphically. The continuous function representing mortality in apopulation is known as a survival curve. Survival curves for the controlgroup and treatment group are represented in FIG. 1.

[0176] The survival curves show that more mature sheep were alive in thetreatment group than the control group at any time. This occurred withthe consumption of normal physiological volumes of water (as aqueousmetal bicarbonate solution).

[0177] The consumption of aqueous metal bicarbonate solution, extendsthe maximum life span of mammals by at least twenty percent andincreases the number of mature mammals alive at any time.

[0178] Senescence in mammals is characterised by progressive oxidationsof the structural and function molecules that constitute body cells andtissues. These oxidations occur particularly in nucleic acids, proteinamino acids and cell membrane lipids.

[0179] Because protons often participate in biological redox reactions,oxidations of many structural and functional molecules in body cells andtissues are increased in rate by the presence of excess protonconcentrations. Oxidations of structural and functional molecules areincreased in rate by acidic conditions.

[0180] In general, oxidations of molecules are linked to protonconcentrations described by a formulation of the Gibbs energy equation

E_(pH)=E_(m)+2.3 RT/F log ([oxidised]/[reduced])

[0181] where E_(pH) is a measure of oxidising power at a particular pHvalue and E_(m) is the mid-point potential. In practice, E_(pH) isdecreased by between −30 mV and −60 mV for each decrease in protonconcentration by a factor of 10. That is, oxidising power is decreasedby between −30 mV and −60 mV for each increase in pH value by 1 pH unit.

[0182] Oxidations of nucleic acids and protein amino acids lead tonucleic acid and protein degradation respectively. These degradationslead to senescence in mammals. Nucleic acid degradation is manifested byeither cell death or cell transformation to the cancerous state. Proteindegradation is manifested by increased urea concentrations in the bodywhich can be detected in the plasma.

[0183] Determination of plasma urea concentrations in elderly mammals isa direct measure of amino acid oxidation, protein degradation andoverall nitrogen (anabolic/catabolic) balance. Determination of plasmaurea concentrations in elderly mammals is a direct measure of cellulardegenerations and senescence.

[0184] Over several years, plasma urea concentrations were determinedfor the control group and the treatment group. Plasma ureaconcentrations are given below: Mean plasma urea concentrations inelderly sheep (mmol per litre) Age (years) Control Group Treatment Group8 11 5 10 13 3 12 13 7

[0185] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases amino acidoxidations, decreases protein degradation and improves overall nitrogen(anabolic/catabolic) balance in mammals. The consumption of aqueousmetal bicarbonate solution, principally magnesium bicarbonate solution,delays cellular degenerations and senescence in mammals.

[0186] Autopsies were performed on sheep, when conditions permitted,within 24 hours of death. Macroscopic signs of significant degenerativediseases and other diseases were recorded. Significant pathology isgiven below: Prevalence of pathology at autopsy (%) MacroscopicSignificant Pathology Control Group Treatment Group (* most significant)(42 autopsies) (38 autopsies) Lungs 24% 21% *Heart 29% 11% Liver 43% 21%Kidney 24% 16% Other Genito-urinary 17% 16% Lymph nodes 40% 37%Intestinal tract 10%  8% *Joints 43%  5% *Bone 24%  3% Teeth 71% 40%*Skin-wool 48% 21% Cancer 12%  3%

[0187] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases the prevalence ofjoint pathology (arthritis) and bone pathology (osteoporosis) andcardiac pathology and skin pathology most significantly and decreasesthe overall prevalence of the pathology of most organs.

EXAMPLE 4 An Experiment to Distinguish Between the Consumption ofMagnesium Bicarbonate and the Consumption of Magnesium Cations Per Se inIncreasing Longevity in a Mammal

[0188] An experiment was conducted to assess if the consumption ofmagnesium bicarbonate increased longevity in a mammal compared to theconsumption of magnesium cations per se. A short-lived mammalian specieswas chosen. Short-lived mammals possess high levels of proton leakacross inner mitochondrial membranes, high levels of carbonic anhydraseenzyme activities (for acid production) and high levels of spontaneouscancer development and spontaneous death. Any increase in longevity in ashort-lived species is indicative of an improvement in fundamental cellbiochemistry. Two hundred outbred (Swiss) female mice were dividedrandomly at weaning into two groups of 100 mice and were maintainedunder identical management and environmental conditions.

[0189] One group of mice was supplied with drinking water that consistedof aqueous metal bicarbonate solution with a pH value between pH 8.1 andpH 8.5. The aqueous metal bicarbonate solution contained approximatelyMg²⁺ 120 mg per litre, Na⁺ 135 mg per litre and HCO₃ ⁻ 950 mg per litre.The major component of the solution was magnesium bicarbonate Mg(HCO₃)₂720 mg per litre approximately. The second group of mice was suppliedwith drinking water that contained magnesium sulphate (Epsom salts) 1gram per litre with a pH value between pH 6.5 and pH 7.0. This drinkingwater contained approximately Mg²⁺ 120 mg per litre. Bicarbonate anionswere absent.

[0190] Both groups of mice were fed commercial laboratory food thatcontained 1 grain of magnesium per kilogram of food. Both groups of micewere fed on alternate days with no food available on the other days.Group-specific drinking water (as described above) was available at alltimes. Feeding on alternate days decreased the possible loss ofbicarbonate anions by stomach acid and food ingesta.

[0191] Results of the experiment are given below: Fifty Percent SurvivalGroup consuming magnesium bicarbonate 790 days Group consuming magnesiumsulphate 736 days Maximum Life Span Group consuming magnesiumbicarbonate 1152 days Group consuming magnesium sulphate 1040 days

[0192] The group of mice consuming aqueous metal bicarbonate solutionhad longevity increased by ten percent compared to the group of miceconsuming magnesium cations per se.

[0193] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, extends the maximum lifespan of mammals by ten percent more than the consumption of magnesiumcations per se

EXAMPLE 5 An Experiment to Decrease the Clinical Signs of Osteoarthritis

[0194] Osteoarthritis is a disease of degeneration. There is degradationand inflammation of the joints of the body. Osteoarthritis is defined asa disease process involving a disturbance of the normal balance ofdegradation and repair in the articular cartilage and subchondral boneof joints. This disturbance of balance causes areas of morphologicaldamage and results in clinical problems such as pain and disability.Osteoarthritis is manifested as a slowly progressive degeneration of thejoints of the hands and large weight-bearing joints (hips and knees). Itis common in post menopausal women. Osteoarthritis is characterised bypain, enlargement of joints and limitation of joint movements. Thelinings of osteoarthritic joints show a moderate to marked degree ofinflammation. The principle pathological changes associated withosteoarthritis are destruction of joint cartilage and neoformations ofbone at joint margins (osteophytes). In osteoarthritis, destruction ofjoint cartilage is caused by acid protease enzymes (and other enzymes)derived often from the lysosomes of cartilage cells (chondrocytes),inflammatory cells and other cells.

[0195] Acid protease enzymes possess optimal activity in an acidicenvironment; that is, an environment with high proton concentrations.Proton concentrations involved in the pathogenesis of osteoarthritisderive from the hydration of carbon dioxide catalysed by intracellularcarbonic anhydrase enzymes. The production of protons by carbonicanhydrase enzymes call be represented by the equation

[0196] Protons formed by carbonic anhydrase enzymes are concentrated byintracellular V-type proton pumps and stored in the endosomes andlysosomes of body cells.

[0197] Functional endosomes and lysosomes maintain internalconcentrations of protons which give them internal pH values between pH3.0 and pH 6.0. Many degenerative diseases, including osteoarthritis,involve intracellular and extracellular release of lysosomal enzymes. Inosteoarthritis, chemical fluxes through the reactions catalysed bylysosomal enzymes result in the breakdown of cartilage and bone.

[0198] An experiment was conducted to assess if the clinical signs ofosteoarthritis could be decreased by the consumption of aqueous metalbicarbonate solution. The clinical signs of osteoarthritis include pain,swelling, inflammation, skill discoloration, joint deformities anddecrease in joint function. An increase in extracellular andintracellular bicarbonate anion concentrations would decrease theproduction of protons from reactions catalysed by carbonic anhydraseenzymes, decrease the pumping of protons by V-type proton pumps,decrease the activities of acid protease enzymes and decrease otheractivities of lysosomes. The clinical signs of osteoarthritis would bealleviated. A group of ten people were chosen who had been diagnosedwith having osteoarthritis. Each person in the group had been sufferingfrom (clinical) osteoarthritis for between 2 and 5 years. Five of thegroup were post menopausal women who had clinical signs ofosteoarthritis in the joints of their hands. The osteoarthritic jointsincluded the distal and proximal interphalangeal joints of the fingersand the carpometacarpal joint of the thumbs. In all 5 cases, loss ofjoint function was moderate to severe.

[0199] In all 5 cases, the women suffered pain, swelling of the fingersand loss of joint movement. Mucous cysts were associated with distaljoint osteoarthritis. Lateral deformities occurred in some proximaljoints with severe loss of joint function. Women with affected thumbshad considerable loss of function and considerable pain. Many hands were“claw-like” in appearance (FIG. 2). The remainder of the group hadosteoarthritis in the hips and knees. These people suffered pain andmoderate loss of joint functions.

[0200] The people consumed aqueous metal bicarbonate solution with a pHvalue between pH 8.1 and 8.5. The aqueous metal bicarbonate solutioncontained approximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre andHCO₃ ⁻ ⁹⁵⁰ mg per litre. The major component of the solution wasmagnesium bicarbonate Mg(HCO₃)₂ 720 mg per litre approximately.

[0201] Consumption of the aqueous metal bicarbonate solution wascommenced at half a litre per day and increased by increments over aperiod of one month to between 2 to 3 litres per day. Consumptionoccurred on an empty stomach to avoid the loss of bicarbonate by stomachacid (HCl). Consumption occurred in small amounts (300 ml) at set timeseach day to avoid rapid increases in bicarbonate concentrations of bodyfluids and to avoid over hydration.

[0202] The results of the experiment were unequivocal. Within 3 to 6months, all participants in the experiment demonstrated substantialdecreases in the clinical signs of osteoarthritis.

[0203] In all cases, there were remissions in the clinical signs ofosteoarthritis which were quantifiable by standard tests of movement,flexibility and strength. The participants showed considerable increasesin joint functions and decreases in acute and chronic joint swellings.The “stabbing” pain or osteoarthritis was alleviated. Some participantshad remissions of inflammation and arthritis to the stage where manychronic swellings were no longer observable and joint mobilities andfunctions were restored (FIG. 3).

[0204] People in the experiment consumed aqueous metal bicarbonatesolution continuously for at least 2 years. During this period, therewas evidence of progressive improvement in healing processes. Mucouscysts associated with distal joint osteoarthritis were no longervisible.

[0205] Remissions in the clinical signs of osteoarthritis weremaintained only with the continual consumption of aqueous metalbicarbonate solution. Once the consumption of aqueous metal bicarbonatesolution was halted, clinical signs of pain and swelling began toreappear within 10 days. Clinical signs again went into remission uponcontinuation of consumption of aqueous metal bicarbonate solution.

[0206] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, results in remissions in theclinical signs of osteoarthritis.

EXAMPLE 6 An Experiment to Maintain and Improve Motor Activity inMammals. An Experiment to Decrease Fatigue and Lethargy and ImproveMotor Activity. An Experiment to Decrease the Fatigue and Lethargy ofChronic Disease and Improve Motor Activity

[0207] Mammals convert food energy into chemical energy that can be usedby body cells to maintain essential cell processes and cell functions.The main chemical energy in mammalian body cells is the chemical ATP(adenosine triphosphate). ATP is synthesised mainly in the mitochondriaof body cells. Mitochondrial ATP production is linked intimately to therespiration rates of mitochondria. The respiration rates of mitochondriaare dependent on many factors including the proton concentrations (pHvalues) of the cytoplasm of body cells. If the intracellular bicarbonatebuffer of mammalian body cells is not maintained, and is not functional,proton concentrations increase in the cytoplasm and the pH value of thecytoplasm decreases. When proton concentrations increase in thecytoplasm sufficiently (pH value decreases sufficiently) the respirationrates of mitochondria are diminished. When the respiration rates ofmitochondria are diminished, the production of ATP is diminished. Whenthe production of ATP is diminished, ATP concentrations in the celldecrease and the main chemical energy source for mammalian body cellsbecomes depleted. Under these conditions, body cells cannot maintainessential cell processes and cell functions. The body becomes fatiguedand lethargic.

[0208] In addition to the hydration of carbon dioxide per se, one of thesources of increased proton concentrations in the cytoplasm of bodycells is the hydrolysis of ATP. The hydrolysis of ATP can be representedby the chemical equation

ATP+H₂O

ADP+P_(i)+H⁺

[0209] Increased proton concentrations from the hydrolysis of ATP occurparticularly in the cytoplasm of muscle cells during muscular (motor)activity. This is referred to often as an increase in ‘lactic acid’ (thelactic acid is, in fact, lactate derived from glycolysis and the ‘acid’is the protons derived from ATP hydrolysis).

[0210] An experiment was conducted to assess if motor activity could bemaintained and improved in mammals by improving the buffering capacityof the extracellular and intracellular bicarbonate buffers.

[0211] Two hundred inbred (Balb c) female mice were divided randomly atweaning into two groups of 100 mice and maintained under identicalconditions for 3 years. Control groups of mice were given drinking waterthat was deionised and slightly acidic (pH 5.0). Treatment groups ofmice were given drinking water that consisted of aqueous metalbicarbonate solution with a pH value between pH 8.1 and 8.5. The aqueousmetal bicarbonate solution contained approximately Mg²⁺ 120 mg perlitre, Na⁺ 135 mg per litre and HCO₃ ⁻ 950 mg per litre. The majorcomponent of the solution was magnesium bicarbonate Mg(HCO₃)₂ 720 mg perlitre approximately.

[0212] Motor activity in mice was assessed at regular intervals for a 12month period between 1 year and 2 years of age. Results of theexperiment are given below: Mean motor activity in mice Control GroupTreatment Group Mean number of mice per hour 26 95 climbing to lid ofcage Mean number of mice per hour 48 82 engaged in exploratory activityMean time to exhaustion during 5 minutes 9 minutes enforced motoractivity

[0213] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, maintains and improves motoractivity in mammals.

[0214] Mitochondria are described as ‘efficient’ if they maintainsufficient production of ATP for maintenance of essential cell processesand cell functions. Efficient mitochondria are the mitochondria of youngmammals.

[0215] In mammals, there are declines in the efficiencies ofmitochondria which are correlated to chronological age. The capacitiesof cells to maintain their particular energy requirements are diminishedprogressively with chronological age. Cells that are unable to meettheir particular energy requirements undergo senescence, becomenon-functional and decline progressively towards cell death. This ismanifested by body senescence and ageing. Mitochondria are described as‘inefficient’ if they cannot maintain the necessary production of ATPfor maintenance of essential cell processes and cell functions.Mitochondrial inefficiency arises from oxidative damage to mitochondrialnucleic acids, mitochondrial enzymes and mitochondrial membrane proteinsand lipids. Inefficient mitochondria gradually and progressivelydominate in body cells through middle age to old age. Middle aged andelderly mammals are fatigued and lethargic relative to the young. Normalbody cells attempt to produce buffers that maintain a cytoplasmic pHvalue of about pH 7.2. In vitro, if mitochondria are placed for a periodin a medium either with an improved buffer at pH 7.2 or with a pH valuebuffered slightly higher than pH 7.2, there occurs an increase inmitochondrial respiration rate and an increase in the production of ATP.

[0216] An experiment was conducted to assess if fatigue and lethargycould be decreased and motor activity improved by improving thebuffering capacity of the cytoplasmic bicarbonate buffer in a group ofmiddle aged and elderly people.

[0217] Improving the buffering capacity of the cytoplasmic bicarbonatebuffer would increase mitochondrial respiration rate and increase theproduction of ATP. Mitochondria would become more ‘efficient’. Morechemical energy would be available for maintenance of essential cellprocesses and cell functions. Fatigue and lethargy would decrease andmotor activity would improve.

[0218] A group of nineteen people were chosen, with a mean age of 61years, who had a history of fatigue and lethargy. In the context of thisexperiment, fatigue and lethargy were determined as subjective feelingsof general exhaustion which were manifested by mild to moderate lack offunction. The people consumed aqueous metal bicarbonate solution with apH value between pH 8.1 and 8.5. The aqueous metal bicarbonate solutioncontained approximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre andHCO₃ ⁻ 950 mg per litre. The major component of the solution wasmagnesium bicarbonate Mg(HCO₃)₂ 720 mg per litre approximately.

[0219] Consumption of the aqueous metal bicarbonate solution wascommenced at half a litre per day and increased by increments over aperiod of one month to between 2 to 3 litres per day. Consumptionoccurred on an empty stomach to avoid the loss of bicarbonate by stomachacid (HCl). Consumption occurred in small amounts (300 ml) at set timeseach day to avoid rapid increases in bicarbonate concentrations of bodyfluids and to avoid over hydration.

[0220] The results of the experiment were unequivocal. Within 3 months,all participants in the experiment demonstrated substantial decreases infatigue and lethargy. All participants described a feeling of well-being(mild euphoria). All participants demonstrated an increased capacity formild physical activity; an improvement in motor activity. Function wasrestored.

[0221] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases fatigue andlethargy and improves motor activity in middle aged and elderly people.

[0222] Chronic disease (including degenerative disease) is manifestedoften by chronic fatigue and lethargy and chronic pain. This is theparticularly for chronic inflammatory diseases and autoimmune diseases.

[0223] The fatigue, lethargy and pain of chronic disease are correlatedoften to the high proton concentrations involved in the pathogenesis ofchronic disease. In addition to the hydration of carbon dioxide per se,proton concentrations involved in the pathogenesis of chronic diseasederive from the hydration of carbon dioxide catalysed by intracellularcarbonic anhydrase enzymes. The production of protons by carbonicanhydrase enzymes can be represented by the equation

[0224] Protons formed by carbonic anhydrase enzymes are concentratedoften by V-type proton pumps and stored in endosomes and lysosomes inthe cell. The breakdown of endosomes and lysosomes createsconcentrations of protons in the cell cytoplasm. This lowers the pHvalue of the cytoplasm and decreases the production of ATP inmitochondria. Cells become energy deficient. Cells are unable tomaintain essential cell processes and cell functions, the body becomesfatigued and lethargic.

[0225] Functional endosomes and lysosomes maintain internalconcentrations of protons which give them internal pH values between pH3.0 and pH 6.0. Many of the chronic and degenerative diseases of thebody involve intracellular lysosomal activities and intracellular andextracellular release of lysosomal enzymes. Chemical fluxes through thereactions catalysed by lysosomal enzymes result in the breakdown ofcells and tissues. Many lysosomal enzymes require low pH values foroptimal activity. Some of these enzymes are known as acid proteaseenzymes.

[0226] Lysosomes located in cells known as macrophages, and in someother cells, are involved in antigen processing and antigenpresentation. Antigen processing and presentation leads to cell to cellinteractions within the immune system which triggers release of a set ofchemicals called cytokines. Cytokine concentrations in the body arecorrelated often to many of the clinical signs of inflammation anddisease. These clinical signs include heat, swelling, pain, fatigue andlethargy.

[0227] An experiment was conducted to assess if fatigue and lethargycould be decreased and motor activity improved by improving thebuffering capacity of the cytoplasmic bicarbonate buffer in a group ofpeople diagnosed and suffering with chronic disease.

[0228] Improving the buffering capacity of the cytoplasmic bicarbonicbuffer would decrease the hydration of carbon dioxide per se, woulddecrease the production of protons from reactions catalysed by carbonicanhydrase enzymes, decrease the pumping of protons by V-type protonpumps, decrease the activities of acid protease enzymes, decrease theactivities of lysosomes, decrease antigen processing and presentation,and increase the production of ATP. Fatigue and lethargy would decreaseand motor activity would improve. Some of the clinical signs of chronicdisease would be alleviated.

[0229] A group of twenty three people were chosen who had been diagnosedwith having chronic disease. Each person had been suffering from chronicdisease for between 3 and 8 years. The diseases consisted of chronicviral diseases, chronic inflammatory diseases and autoimmune diseasesand included rheumatoid arthritis and dermatitis. All people had ahistory of fatigue and lethargy In the context of this experiment,fatigue and lethargy were determined as subjective feelings of generalexhaustion which were manifested by moderate to severe lack of function.The people consumed aqueous metal bicarbonate solution with a pH valuebetween pH 8.1 and 8.5. The aqueous metal bicarbonate solution containedapproximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre, K⁺ 100 mg perlitre and HCO₃ ⁻ 1,100 mg per litre. The major component of the solutionwas magnesium bicarbonate Mg(HCO₃)₂ 720 mg per litre approximately.Potassium bicarbonate 250 mg per litre was a component of the aqueousmetal bicarbonate solution to improve the co-transport of bicarbonateanions into body cells. Consumption of the aqueous metal bicarbonatesolution was commenced at half a litre per day and increased byincrements over a period of one month to between 2 to 3 litres per day.Consumption occurred on an empty stomach to avoid the loss ofbicarbonate by stomach acid (HCl). Consumption occurred in small amounts(300 ml) at set times each day to avoid rapid increases in bicarbonateconcentrations of body fluids and to avoid over hydration.

[0230] The results of the experiment were delayed but unequivocal.Within 3 to 9 months, all participants in the experiment demonstratedsubstantial decreases in fatigue and lethargy. All participantsdemonstrated an increased capacity for mild physical activity; animprovement in motor activity. Function was improved. Those participantswith chronic rheumatoid disease (rheumatoid arthritis) demonstrated somedecreases in inflammation and some decreases in pain. Those participantswith chronic skin disease (dermatitis) demonstrated decreases ininflammation. Those participants with tissue calcification demonstrateddecreases in calcium deposits.

[0231] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases fatigue andlethargy and improves motor activity in people suffering with chronicdisease.

[0232] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases clinical signs ofinflammation and pain and calcification in people suffering with chronicdisease.

EXAMPLE 7 An Experiment to Prevent and to Treat the Clinical Signs ofDiseases Caused by Viruses that Require Proton Concentrations forInfectivity

[0233] Many viruses become infective by utilising high intracellularproton concentrations in host cells. Proton concentrations involved inthe infectivity of viruses, and the pathogenesis of viral diseases,derive from the hydration of carbon dioxide catalysed by intracellularcarbonic anhydrase enzymes. The production of protons by carbonicanhydrase enzymes can be represented by the equation

[0234] Protons formed by carbonic anhydrase enzymes are concentrated byintracellular V-type proton pumps and stored in the endosomes andlysosomes of body cells. Functional endosomes and lysosomes maintaininternal concentrations of protons which give them internal pH valuesbetween pH 3.0 and pH 6.0.

[0235] Virus infectivity often requires the activities of acid proteaseenzymes. Acid protease enzymes are enzymes that function optimally atacidic pH levels. Acid protease enzymes are located in endosomes andlysosomes of body cells.

[0236] Influenza viruses require acid protease enzyme activities fortheir replication and infectivity. The acid proteases of lysosomes andendosomes in body cells act to liberate the nucleic acid (RNA) of theinfluenza virus from the outer viral membrane.

[0237] Many viruses contain their own acid-dependent enzymes whichutilise proton concentrations in host cells. For example, the acidproteases of lentiviruses are required for virus protein assembly andviral infectivity.

[0238] An experiment was instigated with the aim of preventing andtreating the clinical signs of diseases caused by viruses that requireproton concentrations for infectivity. Natural infections with influenzaviruses and flu-like respiratory viruses were taken as the modelinfections. Influenza is an acute febrile infectious respiratory diseasemanifested by inflammation of the bronchial mucosa. It is complicatedoften by bacterial pneumonia. Clinical signs of influenza includeinitially fever, malaise, headache and muscle pain followed by coughing,sneezing and respiratory tract effusions. Flu-like respiratory virusescause respiratory diseases manifested generally by clinical signs ofless intensity than influenza.

[0239] Twenty people were chosen and divided into two equal groups. Thecontrol group did not consume aqueous metal bicarbonate solution. Thetreatment group consumed aqueous metal bicarbonate solution with a pHvalue between 8.1 and 8.5. The aqueous metal bicarbonate solutioncontained approximately Mg²⁺ 120 mg per litre, Na⁺ 135 mg per litre andHCO₃ ⁻ 950 mg per litre. The major component of the solution wasmagnesium bicarbonate Mg(HCO₃)₂ 720 mg per litre approximately.Consumption of the aqueous metal bicarbonate solution was commenced athalf a litre per day and increased by increments over a period of onemonth to between 2 to 3 litres per day. Consumption occurred on an emptystomach to avoid the loss of bicarbonate by stomach acid (HCl).Consumption occurred in small amounts (300 ml) at set times each day toavoid rapid increases in bicarbonate concentrations of body fluids andto avoid over hydration.

[0240] Aqueous metal bicarbonate solution was consumed by people in thetreatment group for 2 years.

[0241] People in both groups worked either in child care centres or inhomes for the elderly and were exposed to influenza and otherrespiratory infections over a 2 year period. Clinical signs of influenzaand flu-like virus infections were observed and recorded over the 2years. Results are given below: Record of influenza and flu-like virusinfections over a 2 year period Control Group Treatment Group InfluenzaNumber of infections 8 2 Duration of symptoms 5 to 10 days  2 to 3 daysSeverity of symptoms (0 to 4) 4 1 to 2 Flu-like viruses Number ofinfections 15  3 Duration of symptoms 3 to 7 days 2 to 3 days Severityof symptoms (0 to 4) 2 to 4 1 to 2

[0242] People consuming aqueous metal bicarbonate solution had a lowerprevalence of the clinical signs of influenza and flu-like virusinfections than people not consuming aqueous metal bicarbonate solution.People consuming aqueous metal bicarbonate solution had less severesymptoms and shorter duration of symptoms than people not consumingaqueous metal bicarbonate solution.

[0243] The consumption of aqueous metal bicarbonate solution,principally magnesium bicarbonate solution, decreases the prevalence ofthe clinical signs of diseases caused by viruses that require protonconcentrations for infectivity.

[0244] The consumption of aqueous metal bicarbonate solution,principally magnesium, bicarbonate solution, decreases the severity andthe duration of the clinical signs of diseases caused by viruses thatrequire proton concentrations for infectivity.

EXAMPLE 8 Suitable Formulation and Range of Parameters and Range ofAdministration Volumes for the Aqueous Metal Bicarbonate Solution

[0245] A suitable formulation for the aqueous metal bicarbonate solutioncontains Mg(HCO₃)₂ 720 mg per litre approximately (Mg²⁺ 120 mg per litreand HCO₃ ⁻ 600 mg per litre approximately). The formulation usuallycontains also NaHCO₃ 485 mg per litre approximately (Na⁺ 135 mg perlitre and HCO₃ ⁻ 350 mg per litre approximately). The pH of theformulation is pH 8.3. The formulation is stored either at 5° C. to 10°C. at 1 atmosphere in a sealed container or at higher temperatures athigher pressures. The formulation is administered or consumed by amammalian (typically human) user in 300 ml doses approximately 6 to 10times per day usually on an empty stomach at approximately equal timeintervals throughout the day. Usually the total amount of formulationusually administered is 1.8 to 3 litres per day.

[0246] The parameters of a suitable formulation for the aqueous metalbicarbonate solution may be conveniently represented as follows: Typicalparameter range Specific parameters Mg(HCO₃)₂ 150 mg/litre to saturationMg(HCO₃)₂ 720 mg/litre solubility per litre (Mg²⁺ 120 mg/litre and HCO₃⁻ 600 mg/litre) NaHCO₃ 0 to 1,000 mg/litre NaHCO₃ 485 mg/litre (Na⁺ 135mg/litre and HCO₃ ⁻ 350 mg/litre pH 8.0 to 8.5 pH 8.3 0° C. to 10° C. at1 atmosphere 5° C. to 10° C. at 1 atmosphere 300 ml dose approximately 1to 15 300 ml dose approximately times per day 6 to 10 times per day

[0247] There exists a range of combinations and concentrations of metalcations that may be included in the suitable formulation of the aqueousmetal bicarbonate solution. There exists a range of anions (other thanbicarbonate) that may be included in stoichiometric amounts with metalcations in the suitable formulation of the aqueous metal bicarbonatesolution. There exists a range of concentrations of bicarbonate anionsthat may be included in stoichiometric amounts with metal cations in thesuitable formulation of the aqueous metal bicarbonate solution.

[0248] A typical range of parameters that may be combined and includedin the suitable formulation of the aqueous metal bicarbonate solutionmay be conveniently represented as follows: Final Concentration inSolution Typical parameter range Specific parameters Mg²⁺   50 to 500mg/litre 120 to 300 mg/litre Na⁺  50 to 1,000 mg/litre 120 to 300mg/litre K⁺   50 to 500 mg/litre 120 to 300 mg/litre Ca²⁺   50 to 500mg/litre 120 to 300 mg/litre HCO₃ ⁻ 200 to 3,000 mg/litre 600 to 2,000mg/litre   Anions other than Stoichiometric with metal cationconcentrations HCO₃ ⁻(eg. Cl⁻, SO₄ ²⁻)

[0249] There exists a range of pH values for the suitable formulation ofaqueous metal bicarbonate solution (that includes cation and anionparameter ranges above). The pH values may be conveniently representedas follows: Typical pH range Specific pH range pH 7.5 to 8.8 pH 8.0 to8.5

[0250] Above pH 8.5, the solution tends to become cloudy due to theformulation of metals carbonates (CO₃ ²⁻).

[0251] There exists a range of physical parameters for the suitableformulation of aqueous metal bicarbonate solution (that includes cationand anion parameter ranges above). The physical parameters may beconveniently represented as follows: Typical parameter range Specificparameter range 0° C. to 30° C. 5° C. to 10° C. 1 to 3 atmospheres 1atmosphere

[0252] Above 10° C., carbon dioxide leaves solution and the solutiontends to become cloudy (with time) due to the formation of metalcarbonates (CO₃ ²⁻). This may be controlled by increasing the pressureon the solution.

[0253] There exists a range of volumes of administration for thesuitable formulation of metal bicarbonate solution (that includes cationand anion parameter ranges above). The volume of aqueous metalBicarbonate solution administered depends on the purpose for theadministration.

[0254] The administered volumes of aqueous metal bicarbonate solutionmay be conveniently represented as follows: Purpose for administrationTypical volume of aqueous metal range administered bicarbonate solutionto 70 kg human Increased longevity 1 to 2 litres per day (normal anddelay in senescence physiological volume requirement for water intake)Prevention of 1 to 2 litres per day (normal degenerative diseasesphysiological volume requirement for water intake) Treatment ofosteoarthritis 1.8 to 3.0 litres per day Treatment of chronic disease1.8 to 3.0 litres per day Maintain and improve 1.8 to 3.0 litres per daymotor activity Decrease fatigue and lethargy 1.8 to 3.0 litres per dayPrevention and treatment of 1.8 to 3.0 litres per day influenza andother acid-dependent viral diseases

[0255] Aqueous metal bicarbonate solution is administered typically in300 ml doses approximately 6 to 10 times per day at equal time intervalsthroughout the day. Typically, the solution is allowed to stand prior toconsumption until the solution reaches 15° C. to 20° C. (cool roomtemperature).

[0256] A suitable formulation for the aqueous metal bicarbonate solutioncontains Mg(HCO₃)₂ 720 mg per litre at pH 8.3. The formulation usuallycontains also NaHCO₃ 485 mg per litre. The aqueous metal bicarbonatesolution may contain a range of cations and anions within a pH range pH7.5 to 8.8. The aqueous metal bicarbonate solution is administered involumes ranging from 1 to 3 litres per day.

EXAMPLE 9

[0257] Osteoarthritis is a slowly progressive degeneration of the jointsof the hands and large weight-bearing joints (hips and knees).Osteoarthritis is common in post menopausal women. Osteoarthritis ischaracterised by pain, enlargement of joints and limitation of jointmovements. The linings of osteoarthritic joints show a moderate tomarked degree of inflammation. The principle pathological changesassociated with osteoarthritis are destruction of joint cartilage andneoformations of bone at joint margins (osteophytes). In osteoarthritis,destruction of joint cartilage is caused by acid protease enzymes (andother enzymes) derived often from the lysosomes of cartilage cells(chondrocytes), inflammatory cells and other cells.

[0258] For an experimental trial, a group of post menopausal women werechosen who had clinical signs of osteoarthritis in the joints of theirhands. The osteoarthritic joints included the distal and proximalinterphalangeal joints of the fingers and the carpometacarpal joint ofthe thumbs. In all cases, loss of joint function was moderate to severe.

[0259] In all cases, the women suffered pain, swelling of the fingersand loss of joint movement. Mucous cysts were associated with distaljoint osteoarthritis. Lateral deformities occurred in some proximaljoints with severe loss of joint function. Women with affected thumbshad considerable loss of function and considerable pain. Many hands were“claw-like” in appearance. Women consumed magnesium bicarbonatesolution, with added sodium bicarbonate. The women consumed between 2 to3 litres of bicarbonate solution per day. In this solution, themagnesium concentration was approximately 120 mg per litre, sodiumconcentration was approximately 135 mg per litre and bicarbonateconcentration was approximately 950 mg per litre. Consumption wascommenced at half a litre per day and increased by increments over aperiod of one month to 2 to 3 litres per day. Consumption occurred on anempty stomach to a void the loss of bicarbonate by stomach acid.Consumption occurred in small amounts (300 mL) at set times each day toavoid rapid increases in bicarbonate concentrations of body fluids.

[0260] In all cases, there were remissions in the clinical signs ofosteoarthritis which were quantifiable by standard tests of movement,flexibility and strength. The participants showed considerable increasesin joint functions and decreases in acute and chronic joint swellings.The “stabbing” pain of osteoarthritis was alleviated. Some participantshad remissions of inflammation and arthritis to the stage where manychronic swellings were no longer observable and joint mobilities andfunctions were restored. However, these improvements were maintainedonly with the continued consumption of bicarbonate anions. Once theconsumption of bicarbonate anions ceased, clinical signs of inflammationbegan to reappear often within a week.

[0261] The participants commented on an absence of lethargy and thepresence of a feeling of well-being. Magnesium bicarbonate alleviatedthe pain and swelling associated with osteoarthritis.

[0262] None of the participants demonstrated any clinical signs ofinfluenza or other respiratory viral infections over the two year periodof the trial. This occurred despite several of the participants workingin situations where exposure to viral infections was high (nursing homesand child care centres).

EXAMPLES 10

[0263] Influenza is an acute febrile infectious respiratory diseasemanifested by inflammation of the bronchial mucosa. Influenza iscomplicated often by bacterial pneumonia which may be fatal.

[0264] For an experimental trial, a group of men and women were chosenwho worked in situations where exposure to the influenza virus waslikely to occur (nursing homes and child care centres). Each person inthe experimental group consumed magnesium bicarbonate solution, withadded sodium bicarbonate. Each person consumed between 2 to 3 litres ofbicarbonate solution per day. In this solution, the magnesiumconcentration was approximately 120 mg per litre, sodium concentrationwas approximately 135 mg per litre and bicarbonate concentration wasapproximately 950 mg per litre.

[0265] Consumption was commenced at half a litre per day and increasedby increments over a period of one month to 2 to 3 litres per day.Consumption occurred on an empty stomach to avoid the loss ofbicarbonate by stomach acid. Consumption occurred in small amounts (300mL) at set times each day to avoid rapid increases in bicarbonateconcentrations of body fluids.

[0266] Over the two year period of the experimental trial, no person inthe experimental group showed any clinical signs of influenza.

EXAMPLE 11

[0267] A suitable formulation for the aqueous metal bicarbonate solutioncontains 720 mg Mg(HCO₃)₂ per litre (120 mg Mg²⁺ per litre and 600 mgHCO₃ ⁻ per litre approximately) and 485 mg NaHCO₃ per litre (135 mg Na⁺per litre and 350 mg HCO₃ ⁻ per litre approximately). The pH of thisformulation is pH 8.3. This formulation is stored at 5 to 10° C. at 1atmosphere or it can be stored at higher temperatures at higherpressures. This formulation is administered in 300 mL dosesapproximately 6 to 10 times per day. That is the amount of formulationusually administered per day is 1.9 to 3 litres per day.

[0268] The parameters of the formulation may be conveniently representedas follows: Typical Parameter Range Specific Parameters 100 mg -saturation solubility 720 mg Mg(HCO₃)₂ per litre (120 mg Mg(HCO₃)₂ perlitre Mg²⁺ and 600 mg HCO₃ ⁻ per litre) 0-1000 mg NaHCO₃ per litre 485mg NaHCO₃ per litre (135 mg Na⁺ and 350 mg HCO₃ ⁻ per litre) pH 8-8.6,typically 8-8.5 pH 8.3 0-10° C. @ 1 atmosphere 5-10° C. @ 1 atmosphere300 mL dose approximately 1 to 300 mL dose approximately 6 to 10 20times per day times per day

EXAMPLE 12

[0269] Mitochondria are inefficient if they cannot maintain thenecessary production of ATP for maintenance of essential cell processesand cell functions. This inefficiency is due often to functional damageto the mitochondrial inner membrane and other mitochondrial molecules.Inefficient mitochondria are not able to maintain normal carbon,electron and proton fluxes.

[0270] However, in middle age, carbon and electron fluxes may bemaintained by the synthesis of fatty acids in the cytoplasm of bodycells. In body cells of the middle aged, fatty acids can be regarded ascarbon and electron sinks necessary for the maintenance of essentialfluxes; that is, for the maintenance of essential life processes. Thesynthesis of fatty acids utilises ATP. However, the fluxes forproduction of ATP in mitochondria are decreased in middle age. There isa consequent ‘energy’ deficit. The middle aged are flat and lethargicrelative to the young, though they can be regarded as fat by necessity;the necessity of staying alive. In addition to utilisation of cell ATP,the synthesis of fatty acids in body cells adds to the carbon dioxideload of the cells and adds to concentrations of intracellular protons.This occurs because the series of chemical reactions that synthesisefatty acids results in a net utilisation of bicarbonate anions and a netproduction of carbon dioxide and protons. For example, each molecule ofthe fatty acid palmitate that is synthesised by cells utilises sevenmolecules of ATP and seven bicarbonate anions and produces sevenmolecules of carbon dioxide and seven protons. Of course, fatty acidsare oxidised continuously from fat stores in the body which produceseven more carbon dioxide. When excess calories are consumed at anychronological age (and converted to fatty acids) the overall carbondioxide load is considerable. Caloric restricted rodents avoid thisextra carbon dioxide load and, as a consequence, they live longer liveswith delays in the onset of degenerative diseases.

[0271] A trial involving people consuming bicarbonate anions in waterwas conducted. These people were middle aged and overweight andcomplained of tiredness and lethargy. No control group was maintainedfor the duration of the trial (people in an initial control group wereunable to consume the volumes of soft water required). People involvedin the trial were given a series of lectures on the biochemistry ofmitochondrial processes. They were requested to decrease their food(calorie) intake considerably and to avoid dietary fats. Excessiveaerobic exercise was not recommended due to the consequent increase inhunger it produces, the large increase in carbon dioxide concentrationsthat occur with increased aerobic muscle activity and the damage excessactivity does to inefficient mitochondria. Indeed, active muscle cellscontain mitochondria with most nucleic acid damage relative to otherbody cells.

[0272] The trial consisted of each person consuming between two to threelitres per day of a mixture of magnesium bicarbonate and sodiumbicarbonate in water. Bicarbonate concentration was established at amaximum of one gram per litre. (This concentration of bicarbonate iswell within the concentrations in several water sources utilised forhuman consumption in Europe. In these waters however, the bicarbonate isin the form of calcium and sodium bicarbonate and pH values often arenot very alkaline.) Consumption was commenced at half a litre per dayand increased by increments over a period of one month to the maximumconsumption. This start-up schedule avoided any gastrointestinal sideeffects due to the smooth muscle relaxation properties of magnesium.Capillary dilation in the face was apparent in several people (which wasinterpreted by those affected as rosy, healthy cheeks). The capillarydilation may have been due to magnesium or may have been due to adecrease in activity of renin which is an acid protease enzyme from thekidney that is central to the control of blood pressure. (Renin exertsits effects ultimately by constriction of small blood vessels.)

[0273] Each participant in the trial was advised to consume thebicarbonate solution ‘on an empty stomach’. Consumption in this manneravoided the mixing of bicarbonate anions with stomach acid which wouldhave resulted in the loss of bicarbonate. Advice was given also toconsume the solution in small amounts at set times each day. Consumptionin this manner avoided a rapid increase in the bicarbonateconcentrations of body fluids.

[0274] The results were unequivocal. Body weight was lost at about onehalf of a kilogram per week after the initial start-up period wascompleted. Other beneficial effects (more important than weight loss tothe participants in the trial) included the absence of lethargy, thepresence of a feeling of well-being (mild euphoria) and the increasedcapacity for mild physical activity. The participants all commented thattheir ‘energy levels’ had improved and that their outlook on life hadconsequently become more positive.

EXAMPLE 13

[0275] A heart muscle cell contains mitochondria that occupy one quarterof the cell volume. It is natural to expect the heart to be rich inmitochondria when one considers the workload of the heart and itssubsequent requirement for ‘energy’. The consumption of magnesiumbicarbonate may assist in maintaining efficient mitochondria in heartmuscle cells. In the presence of bicarbonate anions, mitochondrialefficiency in heart muscle cells is maintained by processes whichinclude decreases in proton leaks across inner mitochondrial membranes,establishment of proton circuits independent of proton leaks andmaintenance of alkaline pH values in mitochondrial matrixes. In thepresence of bicarbonate anions, mitochondrial damage and mitochondrialfailure are decreased. Efficient mitochondria in heart muscle cellsmaintain ATP production so that the heart remains functional as a vitalorgan.

[0276] There are further beneficial effects to the cardiovascular systemresulting from the consumption of magnesium bicarbonate. First,decreased fatty acid synthesis in body cells results in lowered bodyweight with subsequent reduction in high blood pressure to a normalvalue. Indeed, these effects were observed in people participating inthe trial reported in Example 5. Second, lysosomal enzyme damage toischaemic heart muscle may be prevented or decreased.

[0277] There is unequivocal evidence of correlation that heart disease,senescence, degenerative diseases and death are caused by inefficientmitochondria. Though inefficient mitochondria may not be the only causeof these conditions. There is sufficient evidence however thatsenescence and general degeneration in all species studied, from fungito humans, are correlated to the damage to the complex molecules of themitochondria. For example, the mitochondria of aged people carry nucleicacid and protein defects not observed in the mitochondria of youngpeople. This is true particularly of the mitochondria in muscle, heartand brain cells. Accordingly, it has been proposed that several chronicdiseases common in old age may be related to mitochondrial failure,including heart disease, late-onset diabetes and Parkinson's andAlzheimer's diseases. That is, the gradual loss of efficiency of cellmitochondria results in a diminution of the functional capacity of bodycells with pathological consequences.

[0278] A progressive decline in organ function is characteristic of oldage. Some of the changes that occur as people grow older are:

[0279] 1. The ability to focus the eyes decreases and response time tostimuli becomes slower.

[0280] 2. Cancers in epithelial tissues (skin, lung, colon, mammarygland) become more common.

[0281] 3. Heart disease and widely disseminated atherosclerosis occur.

[0282] 4. Osteoporosis and bone and joint pathology occur.

[0283] 5. Thermoregulation becomes inpaired.

[0284] 6. There is a decline in the ability of body organs such as thereproductive organs, lungs, glandular tissues and kidneys to maintaintheir specialised life processes.

[0285] 7. There is a reduced capacity for surviving haemorrhage.

[0286] 8. There is an increase in autoimmune diseases and chronicinflammatory diseases.

[0287] Relative to their life span of around three years, mice developheart disease, kidney disease, arthritis and cancer at similar stages inlife to humans. In other words, both senescence and the similardegenerative diseases of mice and humans are correlated to thechronological age of each species but cannot be linked causally tochronological age per se. It has been observed in many experiments thatrodents fed caloric restricted diets suffer less from the above diseasesthan control animals. It has been observed also that careful necropsieson diet-restricted rodents often do not reveal any gross or microscopicpathology.

[0288] Mitochondrial proton leak is a contributing cause ofmitochondrial inefficiency and hence a source of senescence anddegenerative diseases in short-lived rodents. Mitochondrial proton leakmay be a source of senescence and degenerative diseases in humans.Because the proton leak in humans is only a fraction of the leak inrodents, humans develop senescence and degenerative diseases at a laterchronological age than rodents.

[0289] It may be possible to prevent inefficient processes inmitochondria in order to extend longevity and to delay degenerativediseases. Exogenous sources of appropriate bicarbonate anions can beabsorbed by body cells to maintain intracellular alkaline pH values andthat alkaline pH values maintain mitochondrial respiration rates andmaintain effective proton concentration gradients across innermitochondrial membranes.

[0290] Intracellular alkaline pH values appear necessary for optimumactivities of many enzymes in body cells. These enzymes includepolymerases, phosphofructokinase and carbonic anhydrase. Enzymes permitlife processes to be perpetuated. Therefore, maintenance of enzymeactivities by maintenance of intracellular alkaline pH values may assistin the perpetuation of longevity.

[0291] The long-term provision of appropriate bicarbonate anions to bodycells maintains efficient mitochondrial function, maintains the DNApolymerase activity of mitochondria and therefore maintains theintegrity of mitochondrial DNA. This latter effect results in accuratesyntheses of the complex functional molecules that are involved inelectron fluxes in mitochondria. Of course, bicarbonate anions willdecrease the proton load per se in body cells with a subsequent decreasein proton damage to other cell molecules and a decrease in the tendencyof oxidation reactions to occur. Decreased oxidations result indecreased DNA mutation and decreased amino acid oxidations. Degenerativediseases are delayed.

Industrial Applicability

[0292] An aqueous metal bicarbonate solution of the invention can bereadily utilised in medicine to prevent and to treat certaininflammatory diseases, degenerative diseases and viral diseases inmammals.

1. An aqueous neutral to mildly alkaline metal bicarbonate solution,comprising metal bicarbonate dissolved in the solution, said metalbicarbonate comprising bicarbonate anions and metal cations, and a pHadjusting agent in the solution in an amount whereby the solution is ata neutral to mildly alkaline pH.
 2. The aqueous neutral to mildlyalkaline metal bicarbonate solution of claim 1, wherein the metalbicarbonate is selected from the group consisting of magnesiumbicarbonate, sodium bicarbonate, a mixture of sodium bicarbonate andmagnesium bicarbonate, potassium bicarbonate, a mixture of potassiumbicarbonate and magnesium bicarbonate, calcium bicarbonate, a mixture ofcalcium bicarbonate and magnesium bicarbonate, lithium bicarbonate, anda mixture of lithium bicarbonate and magnesium bicarbonate.
 3. Theaqueous neutral to mildly alkaline metal bicarbonate solution of claim1, wherein the bicarbonate anions are 150 mg to 3500 mg per litre of thesolution.
 4. The aqueous neutral to mildly alkaline metal bicarbonatesolution of claim 1, wherein the metal cations are 30 mg to 500 mg perlitre of the solution.
 5. The aqueous neutral to mildly alkaline metalbicarbonate solution of claim 1, wherein a stoichiometric concentrationof metal cations is in association with the bicarbonate anions.
 6. Theaqueous neutral to mildly alkaline metal bicarbonate solution of claim1, wherein the pH adjusting agent is selected from the group consistingof carbon dioxide, hydrated carbon dioxide, carbonic acid and anymixture thereof.
 7. The aqueous neutral to mildly alkaline metalbicarbonate solution of claim 1, wherein the aqueous metal bicarbonatesolution has a pH 7 to 8.6.
 8. The aqueous metal bicarbonate solution ofclaim 1, wherein the aqueous neutral to mildly alkaline metalbicarbonate solution has a pH of 8.0 to 8.6.
 9. The aqueous metalbicarbonate solution of claim 1, wherein the aqueous neutral to mildlyalkaline metal bicarbonate solution has a temperature in the rangeselected from the group consisting of 0 to 25° C., 0 to 20° C., 0.5 to25° C., 0.5 to 20° C., 0.5 to 15° C., 0.5 to 10° C., 0.5 to 9° C., 0.5to 8° C., 0.5 to 7° C., 1 to 20° C., 1 to 15° C., 1 to 10° C., 1.5 to20° C., 1.5 to 15° C., 1.5 to 10° C., 2 to 20° C., 2 to 15° C., 2 to 10°C., 3 to 20° C., 3 to 15° C., 4 to 20° C., 4 to 15° C., 4 to 10° C., 5to 20° C., 5 to 15° C., 6 to 20° C., 6 to 15° C., 6 to 10° C., 7 to 20°C., 7 to 15° C., 7 to 10° C., 8 to 20° C., 8 to 15° C., 8 to 10° C., 9to 20° C., 9 to 15° C., 9 to 10° C., 10 to 15° C., 0 to 15° C., 0 to 10°C., 3° C. to 10° C. and 5° C. to 10° C.
 10. The aqueous neutral tomildly alkaline metal bicarbonate solution of claim 1, wherein the metalbicarbonate comprises a mixture of sodium bicarbonate and magnesiumbicarbonate.
 11. A solution for preventing and/or treating certaininflammatory diseases and/or degenerative diseases and/or certain viraldiseases in a mammal, comprising the aqueous neutral to mildly alkalinemetal bicarbonate solution of claim 1 wherein the metal bicarbonate isin an amount effective to prevent and/or treat said diseases.
 12. Asolution for decreasing and/or treating senescence and/or increasinglongevity in a mammal, comprising the aqueous neutral to mildly alkalinemetal bicarbonate solution of claim 1 wherein the metal bicarbonate isin an amount effective to decrease and/or treat senescence and/orincrease longevity.
 13. A solution for scavenging protons in a mammal,comprising the aqueous neutral to mildly alkaline metal bicarbonatesolution of claim 1 wherein the metal bicarbonate is in an amounteffective to scavenge protons.
 14. A solution for decreasing protonconcentrations in a mammal, comprising the aqueous neutral to mildlyalkaline metal bicarbonate solution of claim 1 wherein the metalbicarbonate is in an amount effective to decrease proton concentrations.15. A solution for decreasing inflammation and inflammatory conditionsin a mammal comprising the aqueous neutral to mildly alkaline metalbicarbonate solution of claim 1 in an amount effective to decreaseinflammation and/or inflammatory conditions.
 16. A solution forincreasing motor activity and/or decrease fatigue in a mammal,comprising the aqueous neutral to mildly alkaline metal bicarbonatesolution of claim 1 in an amount effective to increase motor activity.17. A process of preparing an aqueous neutral to mildly alkaline metalbicarbonate solution comprising bicarbonate anions and metal cations,which process comprises reacting a compound selected from the groupconsisting of metal carbonate, metal carbonate hydroxide, metal oxide,metal hydroxide and any mixture thereof with an effective concentrationof a pH adjusting agent to produce the aqueous neutral to mildlyalkaline metal bicarbonate solution, wherein the pH adjusting agent ispresent in an amount whereby the solution is at a neutral to mildlyalkaline pH.
 18. The process of preparing an aqueous neutral to mildlyalkaline metal bicarbonate solution of claim 17, wherein the pHadjusting agent is selected from the group consisting of carbon dioxide,hydrated carbon dioxide, carbonic acid and any mixture thereof.
 19. Theprocess of preparing an aqueous neutral to mildly alkaline metalbicarbonate solution of claim 17, wherein the metal bicarbonate isselected from the group consisting of magnesium bicarbonate, sodiumbicarbonate, a mixture of sodium bicarbonate and magnesium bicarbonate,potassium bicarbonate, a mixture of potassium bicarbonate and magnesiumbicarbonate, calcium bicarbonate, a mixture of calcium bicarbonate andmagnesium bicarbonate, lithium bicarbonate, and a mixture of lithiumbicarbonate and magnesium bicarbonate.
 20. The process of preparing anaqueous neutral to mildly alkaline metal bicarbonate solution of claim17, wherein the bicarbonate anions are 150 mg to 3500 mg per litre ofaqueous neutral to mildly alkaline metal bicarbonate solution.
 21. Theprocess of preparing an aqueous neutral to mildly alkaline metalbicarbonate solution of claim 17, wherein the metal cations are 30 mg to500 mg per litre of aqueous neutral to mildly alkaline metal bicarbonatesolution
 22. The process of preparing an aqueous neutral to mildlyalkaline metal bicarbonate solution of claim 17, wherein the aqueousneutral to mildly alkaline metal bicarbonate solution has a pH of 7 to8.6.
 23. The process of preparing an aqueous neutral to mildly alkalinemetal bicarbonate solution of claim 17, wherein the aqueous metalbicarbonate solution has a pH of 8.0 to 8.6.
 24. The process ofpreparing an aqueous neutral to mildly alkaline metal bicarbonatesolution of claim 17, wherein the aqueous metal bicarbonate solution hasa temperature in the range selected from the group consisting of 0 to25° C., 0 to 20° C., 0.5 to 25° C., 0.5 to 20° C., 0.5 to 15° C., 0.5 to10° C., 0.5 to 9° C., 0.5 to 8° C., 0.5 to 7° C., 1 to 20° C., 1 to 15°C., 1 to 10° C., 1.5 to 20° C., 1.5 to 15° C., 1.5 to 10° C., 2 to 20°C., 2 to 15° C., 2 to 10° C., 3 to 20° C., 3 to 15° C., 4 to 20° C., 4to 15° C., 4 to 10° C., 5 to 20° C., 5 to 15° C., 6 to 20° C., 6 to 15°C., 6 to 10° C., 7 to 20° C., 7 to 15° C., 7 to 10° C., 8 to 20° C., 8to 15° C., 8 to 10° C., 9 to 20° C., 9 to 15° C., 9 to 10° C., 10 to 15°C., 0 to 15° C., 0 to 10° C., 3° C. to 10° C. and 5° C. to 10° C.
 25. Anaqueous neutral to mildly alkaline metal bicarbonate solution wheneverprepared by the process of claim
 17. 26. A method of preventing and/ortreating certain inflammatory diseases and/or degenerative diseases in amammal in need of such prevention and/or treatment comprisingadministering to said mammal an effective amount of an aqueous neutralto mildly alkaline metal bicarbonate solution of claim
 1. 27. A methodof preventing and/or treating certain viral diseases in a mammal in needof such prevention and/or treatment comprising administering to saidmammal an effective amount of an aqueous neutral to mildly alkalinemetal bicarbonate solution of claim
 1. 28. A method of decreasing and/ortreating senescence and/or of increasing longevity in a mammalcomprising administering to said mammal an effective amount of anaqueous neutral to mildly alkaline metal bicarbonate solution ofclaim
 1. 29. A method of scavenging protons in a mammal comprisingadministering to said mammal an effective amount of a proton scavenger.30. The method of claim 29, wherein said proton scavenger comprises theaqueous neutral to mildly alkaline metal bicarbonate solution ofclaim
 1. 31. The method of claim 29, wherein said proton scavenger is ametal bicarbonate.
 32. A method of decreasing proton concentrations in amammal by altering carbonic anhydrase enzyme reactions in said mammalcomprising administering to said mammal an effective amount of anaqueous neutral to mildly alkaline metal bicarbonate solution ofclaim
 1. 33. A method of decreasing inflammation and/or inflammatoryconditions in a mammal comprising administering to said mammal aneffective amount of an aqueous neutral to mildly alkaline metalbicarbonate solution of claim
 1. 34. A method of increasing motoractivity and/or decreasing fatigue in a mammal comprising administeringto said mammal an effective amount of an aqueous neutral to mildlyalkaline metal bicarbonate solution of claim
 1. 35. The method of anyone of claims 26, 27, 30, 31, 32, 33 or 34, wherein said mammal is humanand said aqueous neutral to mildly alkaline metal bicarbonate solutionis administered to said human on an empty stomach.
 36. The method of anyone of claims 26, 27, 30, 31, 32, 33 or 34, wherein said mammal ishuman, said aqueous neutral to mildly alkaline metal bicarbonatesolution is administered to said human on an empty stomach and the metalbicarbonate comprises a mixture of sodium bicarbonate and magnesiumbicarbonate.
 37. A combination comprising a substantially stable aqueousneutral to mildly alkaline metal bicarbonate solution, comprising metalbicarbonate dissolved in the solution, said metal bicarbonate comprisingbicarbonate anions and metal cations, and a pH adjusting agent in thesolution in an amount whereby the solution is at a neutral to mildlyalkaline pH, in combination with a stabilising agent in an amounteffective to maintain and stabilise the bicarbonate anions in theneutral to mildly alkaline solution.